subject:(glial scar)

University of Arizona

1. Zbesko, Jacob C. Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes .

Degree: 2020, University of Arizona

URL: http://hdl.handle.net/10150/645775

► Stroke affects nearly 800,000 Americans every year and, of survivors, around one third will develop dementia. Not only personally devastating to sufferers, this disease places… (more)

▼ Stroke affects nearly 800,000 Americans every year and, of survivors, around one third will develop dementia. Not only personally devastating to sufferers, this disease places an enormous financial and emotional burden on their loved ones. Currently, the thrombolytic agent Tissue Plasminogen Activator (tPA) is the only Food and Drug Administration (FDA) approved medication for stroke. Thrombolytic therapy with tPA can prevent irreversible injury by restoring blood flow if administered within 6 hours of stroke onset. However, there are no approved therapeutics designed to prevent or treat post-stroke dementia, partly due to our lack of understanding of the mechanism(s) that lead to its development. The goal of this dissertation is to further our understanding of the basic biology of stroke recovery in order to facilitate the development of treatments that prevent or alleviate post-stroke dementia. To accomplish this goal, we investigated the cellular and molecular mechanisms of brain repair by glial scar formation following stroke, as well as the role of T-lymphocytes and Immunoglobulin (Ig) A antibodies in the B-lymphocyte response to stroke. Results from our investigation of glial scar formation indicate that although glial scar astrocytes form a physical and endocytic barrier that encapsulates chronic stroke infarcts, the barrier they form is permeable to the chronic inflammatory response that takes place within the infarct. This leakage allows neurotoxic factors present within the infarct to permeate into the surrounding brain tissue in the weeks following stroke, which correlates with secondary neurodegeneration. Results from our investigation of the role of T-lymphocytes and IgA antibodies in the B-lymphocyte response to stroke indicate that following stroke, B-lymphocytes mature into IgA+ plasma cells through a T-lymphocyte independent mechanism and produce natural antibodies. Together these data indicate that although a role of glial scar astrocytes is to segregate the chronic inflammatory response to stroke from the surviving brain, this function is insufficient to prevent secondary neurodegeneration. They also indicate that a novel role of the B-lymphocyte response to stroke is to produce IgA natural antibodies within the infarct. Natural antibodies are known to be polyreactive to cellular debris and are often associated with the clearance of apoptotic cells and oxidized lipids. We hypothesize that these antibodies, and other neurotoxic factors present within the stroke infarct, enter the surrounding brain tissue through the permeable glial scar causing damage to the surviving brain tissue, suggesting a potential mechanism for the development of post-stroke dementia. Advisors/Committee Members: Wu, Hsin-Jung Joyce (advisor), Doyle, Kristian (advisor), Nikolich-Zugich, Janko (committeemember), Koshy, Anita (committeemember), Morrison, Helena (committeemember).

Subjects/Keywords: B-lymphocyte; Glial scar; Stoke

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APA (6^th Edition):

Zbesko, J. C. (2020). Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes . (Doctoral Dissertation). University of Arizona. Retrieved from http://hdl.handle.net/10150/645775

Chicago Manual of Style (16^th Edition):

Zbesko, Jacob C. “Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes .” 2020. Doctoral Dissertation, University of Arizona. Accessed February 25, 2021. http://hdl.handle.net/10150/645775.

MLA Handbook (7^th Edition):

Zbesko, Jacob C. “Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes .” 2020. Web. 25 Feb 2021.

Vancouver:

Zbesko JC. Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes . [Internet] [Doctoral dissertation]. University of Arizona; 2020. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10150/645775.

Council of Science Editors:

Zbesko JC. Investigating the Chronic Inflammatory Response to Stroke: The Role of Glial Scar Astrocytes and B-Lymphocytes . [Doctoral Dissertation]. University of Arizona; 2020. Available from: http://hdl.handle.net/10150/645775

University of Miami

2. Hackett, Amber. The Role of NG2 Cells after Contusive Spinal Cord Injury.

Degree: PhD, Neuroscience (Medicine), 2016, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/1767

► NG2 cells, also known as oligodendrocyte progenitor cells (OPCs), are tiled throughout the adult central nervous system (CNS) and proliferate and differentiate into oligodendrocytes… (more)

▼ NG2 cells, also known as oligodendrocyte progenitor cells (OPCs), are tiled throughout the adult central nervous system (CNS) and proliferate and differentiate into oligodendrocytes throughout life. After spinal cord injury (SCI), many oligodendrocytes are lost, and promoting oligodendrocyte differentiation is an appealing target to promote functional recovery after SCI. However, in addition to differentiating into oligodendrocytes, NG2 cells proliferate in the glial scar and contribute to axon regeneration failure. NG2 cells are committed to the oligodendrocyte lineage in adult mice. However, in other models of CNS injury, NG2 cells gain the capacity to differentiate into astrocytes. The astroglial fate of NG2 cells after SCI is currently unknown and is important to investigate because astrocytes are major contributors to the glial scar. To trace the fate of NG2 cells after SCI, I used NG2-CreER mice bred to tdTomato, which serves as a Cre reporter. I found that in addition to increasing their proliferation and differentiation into oligodendrocytes after SCI, NG2 cells gain the capacity to differentiate into astrocytes in the glial scar. Mechanisms that underlie these fate changes are not well understood. Since cytokine ligands for the signal transducer and activator of transcription 3 (STAT3) pathway are upregulated after SCI, and have been implicated in NG2 cell and astrocyte fate, I hypothesized that the transcription factor STAT3 might to an important mediator of NG2 cell fate after SCI. To address the role of STAT3 in NG2 cells after SCI, I used tamoxifen inducible NG2 cell specific deletions of either STAT3 or its suppressor, suppressor of cytokine signaling 3 (SOCS3). I have identified STAT3 as an important regulator of efficient oligodendrogenesis after SCI. Surprisingly, I found that SOCS3 deletion led to increased proliferation of NG2 cells via a STAT3 independent mechanism. I also found that neither STAT3 nor SOCS3 affected astrogliogenesis from NG2 cells after SCI. Altogether these data suggest that STAT3 and SOCS3 are important regulators of NG2 cell proliferation and differentiation after SCI. Understanding mechanisms that mediate NG2 cell proliferation and differentiation in the glial scar is essential since NG2 cells are important players in axon regeneration failure after SCI. My data reveal insight into the role of cytokine signaling in both oligodendrogenesis and proliferation of NG2 cells, and could be used to alter glial scar formation or promote remyelination after SCI. Advisors/Committee Members: Jae K. Lee, Nagi G. Ayad, Eleonore Beurel, Pantelis Tsoulfas.

Subjects/Keywords: Spinal Cord Injury; Glial Scar; Oligodendrocytes; Cytokines

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hackett, A. (2016). The Role of NG2 Cells after Contusive Spinal Cord Injury. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/1767

Chicago Manual of Style (16^th Edition):

Hackett, Amber. “The Role of NG2 Cells after Contusive Spinal Cord Injury.” 2016. Doctoral Dissertation, University of Miami. Accessed February 25, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/1767.

MLA Handbook (7^th Edition):

Hackett, Amber. “The Role of NG2 Cells after Contusive Spinal Cord Injury.” 2016. Web. 25 Feb 2021.

Vancouver:

Hackett A. The Role of NG2 Cells after Contusive Spinal Cord Injury. [Internet] [Doctoral dissertation]. University of Miami; 2016. [cited 2021 Feb 25]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1767.

Council of Science Editors:

Hackett A. The Role of NG2 Cells after Contusive Spinal Cord Injury. [Doctoral Dissertation]. University of Miami; 2016. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/1767

University of Miami

3. Freer, Lucy. Macrophage Depletion as a Therapeutic Method After SCI.

Degree: PhD, Neuroscience (Medicine), 2018, University of Miami

URL: https://scholarlyrepository.miami.edu/oa_dissertations/2019

► Developing successful therapies for spinal cord injury (SCI) is a formidable medical challenge in part because of the axonal growth-inhibitory environment that develops following injury… (more)

▼ Developing successful therapies for spinal cord injury (SCI) is a formidable medical challenge in part because of the axonal growth-inhibitory environment that develops following injury characterized by a glial and fibrotic scar [3]. Whereas the glial scar has been an important research focus for many years, less attention has been given to the fibrotic scar. Recent work from our lab has demonstrated that hematogenous macrophages are important for the formation of the fibrotic scar [4]. Depletion of hematogenous macrophages following SCI resulted in reduced fibrotic scar formation and increased growth of axons into the lesion site. In order to identify the signaling pathways responsible for these changes a qPCR array was used to look at the expression of 84 different cytokines and chemokines in macrophage depleted tissue compared to PBS controls. Surprisingly, of the 29 differentially regulated genes identified, the vast majority (26) were upregulated. Many of the upregulated genes were anti-fibrotic and pro-growth factors like VEGF and BMPs. On the other hand, only three genes were downregulated one of them being tumor necrosis factor superfamily member 13 (tnfsf13). Tnfsf13, also known as A Proliferation Inducing Factor (April), has been previously associated with fibrosis thus we tested its role in fibrotic scar formation following SCI using April knockout mice. We identified that April and one of its receptors, Bcma, were significantly upregulated following SCI. Additionally, similar to the macrophage depletion effect, April KO mice had a smaller fibrotic scar and increased axons in the injury site. In addition, April KO mice also had reduced macrophage infiltration and reduced early proinflammatory cytokine expression, suggesting that April indirectly influences the fibrotic scar size via modulation of the inflammatory response. As an alternate strategy towards application of the macrophage depletion effect, we tested the combination of macrophage depletion and Schwann cell transplantation hypothesizing that the macrophage-depleted environment would promote axon growth through the transplant. Macrophage depletion reduced cyst size in Schwann cell transplanted rats; however, axon regeneration through the graft was unaffected and combination of macrophage depletion and Schwann cell transplantation did not improve functional recovery as compared to Schwann cell transplantation alone. Overall, my findings identified a novel mediator of early pro-inflammatory changes following spinal cord injury, April, but disproved the idea that macrophages are a limitation to axon growth through the Schwann cell transplant. Advisors/Committee Members: Jae K. Lee, Abigail Hackam, Robert Keane, Roberta Brambilla, Gerhard Dahl, John C. Gensel.

Subjects/Keywords: Macrophage; Glial Scar; Spinal cord injury; Fibrotic Scar

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Freer, L. (2018). Macrophage Depletion as a Therapeutic Method After SCI. (Doctoral Dissertation). University of Miami. Retrieved from https://scholarlyrepository.miami.edu/oa_dissertations/2019

Chicago Manual of Style (16^th Edition):

Freer, Lucy. “Macrophage Depletion as a Therapeutic Method After SCI.” 2018. Doctoral Dissertation, University of Miami. Accessed February 25, 2021. https://scholarlyrepository.miami.edu/oa_dissertations/2019.

MLA Handbook (7^th Edition):

Freer, Lucy. “Macrophage Depletion as a Therapeutic Method After SCI.” 2018. Web. 25 Feb 2021.

Vancouver:

Freer L. Macrophage Depletion as a Therapeutic Method After SCI. [Internet] [Doctoral dissertation]. University of Miami; 2018. [cited 2021 Feb 25]. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/2019.

Council of Science Editors:

Freer L. Macrophage Depletion as a Therapeutic Method After SCI. [Doctoral Dissertation]. University of Miami; 2018. Available from: https://scholarlyrepository.miami.edu/oa_dissertations/2019

Wayne State University

4. Ereifej, Evon S. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface.

Degree: PhD, Biomedical Engineering, 2012, Wayne State University

URL: https://digitalcommons.wayne.edu/oa_dissertations/436

► Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of… (more)

▼ Neural electrode devices hold great promise to help people with the restoration of lost functions, however, research is lacking in the biomaterial design of a stable, long-term device. Current devices lack long term functionality, most have been found unable to record neural activity within weeks after implantation due to the development of glial scar tissue (Polikov et al., 2006; Zhong and Bellamkonda, 2008). The long-term effect of chronically implanted electrodes is the formation of a glial scar made up of reactive astrocytes and the matrix proteins they generate (Polikov et al., 2005; Seil and Webster, 2008). Scarring is initiated when a device is inserted into brain tissue and is associated with an inflammatory response. Activated astrocytes are hypertrophic, hyperplastic, have an upregulation of intermediate filaments GFAP and vimentin expression, and filament formation (Buffo et al., 2010; Gervasi et al., 2008). Current approaches towards inhibiting the initiation of glial scarring range from altering the geometry, roughness, size, shape and materials of the device (Grill et al., 2009; Kotov et al., 2009; Kotzar et al., 2002; Szarowski et al., 2003). Literature has shown that surface topography modifications can alter cell alignment, adhesion, proliferation, migration, and gene expression (Agnew et al., 1983; Cogan et al., 2005; Cogan et al., 2006; Merrill et al., 2005). Thus, the goals of the presented work are to study the cellular response to biomaterials used in neural electrode fabrication and assess surface topography effects on minimizing astrogliosis. Initially, to examine astrocyte response to various materials used in neural electrode fabrication, astrocytes were cultured on platinum, silicon, PMMA, and SU-8 surfaces, with polystyrene as the control surface. Cell proliferation, viability, morphology and gene expression was measured for seven days in vitro. Results determined the cellular characteristics, reactions and growth rates of astrocytes grown on PMMA resembled closely to that of cells grown on the control surface, thus confirming the biocompatibility of PMMA. Additionally, the astrocyte GFAP gene expressions of cells grown on PMMA were lower than the control, signifying a lack of astrocyte reactivity. Based on the findings from the biomaterials study, it was decided to optimize PMMA by changing the surface characteristic of the material. Through the process of hot embossing, nanopatterns were placed on the surface in order to test the hypothesis that nanopattterning can improve the cellular response to the material. Results of this study agreed with current literature showing that topography effects protein and cell behavior. It was concluded that for the use in neural electrode fabrication and design, the 3600mm/gratings pattern feature sizes were optimal. The 3600 mm/gratings pattern depicted cell alignment along the nanopattern, less protein adsorption, less cell adhesion, proliferation and viability, inhibition of… Advisors/Committee Members: Pamela J. VandeVord.

Subjects/Keywords: astrocytes, biocompatibility, biomaterials, glial scar, nanopatterns, neural electrodes; Biomedical Engineering and Bioengineering

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ereifej, E. S. (2012). Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface. (Doctoral Dissertation). Wayne State University. Retrieved from https://digitalcommons.wayne.edu/oa_dissertations/436

Chicago Manual of Style (16^th Edition):

Ereifej, Evon S. “Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface.” 2012. Doctoral Dissertation, Wayne State University. Accessed February 25, 2021. https://digitalcommons.wayne.edu/oa_dissertations/436.

MLA Handbook (7^th Edition):

Ereifej, Evon S. “Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface.” 2012. Web. 25 Feb 2021.

Vancouver:

Ereifej ES. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface. [Internet] [Doctoral dissertation]. Wayne State University; 2012. [cited 2021 Feb 25]. Available from: https://digitalcommons.wayne.edu/oa_dissertations/436.

Council of Science Editors:

Ereifej ES. Studying the glial cell response to biomaterials and surface topography for improving the neural electrode interface. [Doctoral Dissertation]. Wayne State University; 2012. Available from: https://digitalcommons.wayne.edu/oa_dissertations/436

5. Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi, Mayumi. Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。.

Degree: 博士（医学）, 2016, Nara Medical University / 奈良県立医科大学

URL: http://hdl.handle.net/10564/3282

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OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although… (more)

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OBJECTIVE Transplantation of bone marrow stromal cells (BMSCs) is a theoretical potential as a therapeutic strategy in the treatment of spinal cord injury (SCI). Although a scaffold is sometimes used for retaining transplanted cells in damaged tissue, it is also known to induce redundant immunoreactions during the degradation processes. In this study, the authors prepared cell sheets made of BMSCs, which are transplantable without a scaffold, and investigated their effects on axonal regeneration, glial scar formation, and functional recovery in a completely transected SCI model in rats. METHODS BMSC sheets were prepared from the bone marrow of female Fischer 344 rats using ascorbic acid and were cryopreserved until the day of transplantation. A gelatin sponge (GS), as a control, or BMSC sheet was transplanted into a 2-mm-sized defect of the spinal cord at the T-8 level. Axonal regeneration and glial scar formation were assessed 2 and 8 weeks after transplantation by immunohistochemical analyses using anti-Tuj1 and glial fibrillary acidic protein (GFAP) antibodies, respectively. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan scale. RESULTS The BMSC sheets promoted axonal regeneration at 2 weeks after transplantation, but there was no significant difference in the number of Tuj1-positive axons between the sheet- and GS-transplanted groups. At 8 weeks after transplantation, Tuj1-positive axons elongated across the sheet, and their numbers were significantly greater in the sheet group than in the GS group. The areas of GFAP-positive glial scars in the sheet group were significantly reduced compared with those of the GS group at both time points. Finally, hindlimb locomotor function was ameliorated in the sheet group at 4 and 8 weeks after transplantation. CONCLUSIONS The results of the present study indicate that an ascorbic acid-induced BMSC sheet is effective in the treatment of SCI and enables autologous transplantation without requiring a scaffold.

博士（医学）・甲第656号・平成28年11月24日

The definitive version is available at " http://dx.doi.org/10.3171/2016.8.SPINE16250 "

Subjects/Keywords: bone marrow stromal cell; cell sheet; axonal regeneration; spinal cord injury; ascorbic acid; glial scar

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APA (6^th Edition):

Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi, M. (2016). Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。. (Thesis). Nara Medical University / 奈良県立医科大学. Retrieved from http://hdl.handle.net/10564/3282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi, Mayumi. “Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。.” 2016. Thesis, Nara Medical University / 奈良県立医科大学. Accessed February 25, 2021. http://hdl.handle.net/10564/3282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi, Mayumi. “Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。.” 2016. Web. 25 Feb 2021.

Vancouver:

Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi M. Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。. [Internet] [Thesis]. Nara Medical University / 奈良県立医科大学; 2016. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10564/3282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Okuda, Akinori; Horii-Hayashi, Noriko; Sasagawa, Takayo; Shimizu, Takamasa; Shigematsu, Hideki; Iwata, Eiichiro; Morimoto, Yasuhiko; Masuda, Keisuke; Koizumi, Munehisa; Akahane, Manabu; Nishi M. Bone marrow stromal cell sheets may promote axonal regeneration and functional recovery with suppression of glial scar formation after spinal cord transection injury in rats. : 骨髄間葉系細胞シートはラット脊髄離断損傷後にグリア瘢痕形成を抑制し、軸索再生と後肢運動機能改善を促進する。. [Thesis]. Nara Medical University / 奈良県立医科大学; 2016. Available from: http://hdl.handle.net/10564/3282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

National University of Ireland – Galway

6. Ab Patar, Mohd Nor Azim. Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies .

Degree: 2018, National University of Ireland – Galway

URL: http://hdl.handle.net/10379/7282

► There are several detrimental events that occur in the aftermath of a spinal cord injury (SCI); these include glial scar formation, accumulation of axon growth… (more)

▼ There are several detrimental events that occur in the aftermath of a spinal cord injury (SCI); these include glial scar formation, accumulation of axon growth inhibitors and immune mediators. These events present challenges to SCI repair and therapy development. Ex vivo organotypic slice cultures provide a reliable model platform for the study of cell dynamics and therapeutic intervention following SCI. Four research chapters (chapters 3-6) are presented here. In research chapter 3 of this thesis, three SCI models (stab, contusion and transection injury) were developed to study glial scar formation with a focus on reactive astrocytes and NG2 proteoglycans. Stereological analysis was carried out on scar zone (SZ) and injury zone (IZ) in each model of SCI. The transection injury model was chosen as the best model to study axonal growth after SCI. Ex vivo spinal culture experiments consumed many Millicell® inserts. In chapter 4, we optimised a cheap reproducible method of preparing homemade inserts. Chondroitinase ABC (ChABC) successfully promotes neurite outgrowth and functional recovery after SCI in in vivo rat studies. In chapter 5, the effect of ChABC on the cellular environment was examined after SCI in the SZ, near scar zone (NSZ) and far scar zone (FSZ). We show that ChABC enzymatic treatment causes significant change in the injured microenvironment and may promote axonal regeneration. Lentiviral vectors expressing neurotrophin-3 (NT3) and short hairpin NG2 (shNG2) knockdown were tested in vitro and in ex vivo transected spinal cord slice cultures in chapter 6. NT3 promotes axonal sprouting following SCI. NG2 is upregulated after SCI and inhibits neurite outgrowth. We show that NG2 sh1 causes NG2 knockdown and promotes neurite outgrowth in vitro. Combination treatment of Lenti NT3/NG2 sh1 promotes axonal sprouting at day 7 post transection injury. This study shows how ex vivo spinal cord slices can be used as a platform for studying glial scarring and potential SCI treatments. Advisors/Committee Members: McMahon, Siobhan (advisor), Howard, Linda (advisor).

Subjects/Keywords: Spinal cord injury; Glial scar; Ex vivo slice cultures; Chondroitinase ABC; Lentivirus; Medicine; Anatomy

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ab Patar, M. N. A. (2018). Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies . (Thesis). National University of Ireland – Galway. Retrieved from http://hdl.handle.net/10379/7282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ab Patar, Mohd Nor Azim. “Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies .” 2018. Thesis, National University of Ireland – Galway. Accessed February 25, 2021. http://hdl.handle.net/10379/7282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ab Patar, Mohd Nor Azim. “Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies .” 2018. Web. 25 Feb 2021.

Vancouver:

Ab Patar MNA. Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies . [Internet] [Thesis]. National University of Ireland – Galway; 2018. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10379/7282.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ab Patar MNA. Ex Vivo slice culture model of rat spinal cord injury as a platform for testing proposed treatment strategies . [Thesis]. National University of Ireland – Galway; 2018. Available from: http://hdl.handle.net/10379/7282

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

7. Pakulska, Malgorzata Maria. Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration.

Degree: PhD, 2016, University of Toronto

URL: http://hdl.handle.net/1807/89261

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Spinal cord injury (SCI) is a devastating condition that affects millions of people worldwide. Successful drug therapies for SCI have been difficult to achieve due… (more)

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Spinal cord injury (SCI) is a devastating condition that affects millions of people worldwide. Successful drug therapies for SCI have been difficult to achieve due to the complex nature of the pathology. Increasingly, researchers are moving towards combination strategies using at least two therapeutics that target distinct injury pathways. Furthermore, sustained drug delivery to the spinal cord is complicated by the presence of the blood spinal cord barrier (BSCB) and cerebrospinal fluid flow. In this work, an injectable hydrogel was designed for the minimally invasive, localized, sustained delivery of two different protein therapeutics to the injured spinal cord: chondroitinase ABC (ChABC), an enzyme that degrades the glial scar, and stromal cell-derived factor 1Îą (SDF), a chemokine implicated in the migration of endogenous neural precursor cells (NPC) to the site of SCI. Design of experiment (DOE) was used to explore the relationships between composition and mechanical properties of a physically and chemically crosslinked methylcellulose hydrogel (XMC). An optimal gel formulation that was injectable, minimally swelling, long-lasting, and safe in vivo, was chosen for future studies. Active ChABC was released from XMC for at least 7 days using reversible affinity interactions. Additionally, a mathematical model was developed to provide a mechanistic understanding of affinity-based release systems and allow for rational design. Active SDF was released from XMC for at least 28 days by exploiting electrostatic interactions with negatively charged poly(lactic-co-glycolic acid) nanoparticles (PLGA np). This is the first evidence of long-term protein release using PLGA np without encapsulation. The efficacy of this combined treatment was tested in a rat model of compressive SCI. ChABC treatment resulted in decreased chondroitin sulfate proteoglycan (CSPG) levels for up to two weeks after injury and a trend towards improved behavioural recovery. Treatment with SDF did not improve behavioural nor histological outcomes and did not show any synergy with ChABC. Together these studies introduce XMC as a novel, injectable hydrogel platform for therapeutic protein delivery to the spinal cord and demonstrate two different methods of controlling protein release from this hydrogel.

2018-07-08 00:00:00

Advisors/Committee Members: Shoichet, Molly S, Chemical Engineering Applied Chemistry.

Subjects/Keywords: adult stem cells; chondroitinase abc; CXCL12; drug delivery; glial scar; spinal cord; 0541

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pakulska, M. M. (2016). Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/89261

Chicago Manual of Style (16^th Edition):

Pakulska, Malgorzata Maria. “Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration.” 2016. Doctoral Dissertation, University of Toronto. Accessed February 25, 2021. http://hdl.handle.net/1807/89261.

MLA Handbook (7^th Edition):

Pakulska, Malgorzata Maria. “Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration.” 2016. Web. 25 Feb 2021.

Vancouver:

Pakulska MM. Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration. [Internet] [Doctoral dissertation]. University of Toronto; 2016. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1807/89261.

Council of Science Editors:

Pakulska MM. Combined Delivery of Chondroitinase ABC (ChABC) and Stromal Cell Derived Factor 1α (SDF1α) for Spinal Cord Regeneration. [Doctoral Dissertation]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/89261

University of Toronto

8. Dragas, Rachel. Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth.

Degree: 2018, University of Toronto

URL: http://hdl.handle.net/1807/89622

►

The astroglial scar is a defining hallmark of secondary pathology following central nervous system (CNS) injury that significantly obstructs neuroregeneration. Neural progenitor cell (NPC) therapies… (more)

Subjects/Keywords: central nervous system injury; glial scar; hepatocyte growth factor; neural progenitor cells; reactive astrocytes; regeneration; 0564

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dragas, R. (2018). Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/89622

Chicago Manual of Style (16^th Edition):

Dragas, Rachel. “Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth.” 2018. Masters Thesis, University of Toronto. Accessed February 25, 2021. http://hdl.handle.net/1807/89622.

MLA Handbook (7^th Edition):

Dragas, Rachel. “Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth.” 2018. Web. 25 Feb 2021.

Vancouver:

Dragas R. Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth. [Internet] [Masters thesis]. University of Toronto; 2018. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1807/89622.

Council of Science Editors:

Dragas R. Hepatocyte Growth Factor-Preconditioned Neural Progenitor Cells Attenuate Astrocyte Reactivity and Promote Neurite Outgrowth. [Masters Thesis]. University of Toronto; 2018. Available from: http://hdl.handle.net/1807/89622

Univerzitet u Beogradu

9. Dacić, Sanja A., 1973-. Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova.

Degree: Biološki fakultet, 2014, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:7805/bdef:Content/get

►

Biologija - Neurobiologija / Biology - Neurobiology

Traumatska povreda mozga (TPM) predstavlja veliki zdravstveni problem savremenog društva jer je vodeći uzrok smrti i invaliditeta kod… (more)

▼

Biologija - Neurobiologija / Biology - Neurobiology

Traumatska povreda mozga (TPM) predstavlja veliki zdravstveni problem savremenog društva jer je vodeći uzrok smrti i invaliditeta kod mlađih osoba. Uprkos znatnim istraživačkim i kliničkim naporima, još uvek ne postoji ni jedan dovoljno uspešan terapijski pristup koji utiče na sve patofiziološke procese koji prate moždanu traumu, odnosno, koji može ukloniti sve njene posledice. Stoga se uspešan tretman u borbi protiv TPM danas pokušava pronaći kombinacijom različitih terapijskih tretmana. Poznato je da je oporavak izgubljene funkcije nakon povrede mozga odraslih veoma spor i nepotpun usled nepovratnog uništenja nervnih ćelija i ograničene mogućnosti remodelovanja postojećih i formiranja novih neuronskih veza. Glavna prepreka za uspešniji oporavak posle oštećenja je nepermisivna sredina glijskog ožiljka koji se formira nakon povrede, a koji sprečava izrastanje novih nervnih vlakana i uspostavljanje novih neuronskih veza. Glijski ožiljak čine gusta mreža glijskih ćelija (astrocita i oligodendrocitnih prekursorskih ćelija) i nepropustan vanćelijski matriks (ECM). Cilj ove studije bio je da se ispita dejstvo kompleksa vitamina B (B1, B2, B3, B6 i B12) i ribavirina (RBV, purinskog nukleozidnog analoga) na oporavak motornih funkcija, posle jednostrane ablacije senzomotorne kore (ASK) prednjeg mozga pacova. Mužjacima Wistar soja, starim 2.5 meseca, urađena je ASK prema sledećim koordinatama: 2mm ispred, 4 mm iza bregme i 4 mm lateralno od središnje linije u dubinu do pojave bele mase mozga. Operisane životinje podeljene su, prema tretmanu nakon ASK, u 6 grupa: L grupa – tretirana fiziološkim rastvorom; LK1 grupa – tretirana kombinacijom vitamina B1 (33 mg/kg/dan), B6 (33 mg/kg/dan) i B12 (0,5 μg/kg/dan); LK2 grupa – tretirana kombinacijom vitamina B2 (7,5 mg/kg/dan) i B3 (500 mg/kg/dan); LK grupa – tretirana kombinacijom svih pet vitamina: B1, B2, B3, B6 i B12 u prethodno navedenim dozama; LR grupa – primala je RBV (30 mg/kg/dan); LKR grupa – tretirana kombinacijom svih 5 B vitamina i RBV u prethodno navedenim dozama. Prva injekcija B vitamina data je i.p. 15 minuta nakon ASK, a potom na svaka 24 sata tokom sledećih 14 dana, dok je RBV aplikovan od 3 dana nakon ASK, jednom dnevno do kraja eksperimenta. Uticaj primenjenih tretmana na oporavak nakon ASK praćen je testiranjem ponašanja (test prelaska preko grede - BW test), RT-PCR i Western blot analizom, kao i različitim imunohistohemijskim metodama...

Advisors/Committee Members: Peković, Sanja.

Subjects/Keywords: rat; brain injury; locomotor coordination; reactive astrogliosis; glial scar; neuronal sprouting and branching; synaptic plasticity; chondroitin sulfate proteoglycans; B vitamins; ribavirin

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dacić, Sanja A., 1. (2014). Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:7805/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dacić, Sanja A., 1973-. “Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova.” 2014. Thesis, Univerzitet u Beogradu. Accessed February 25, 2021. https://fedorabg.bg.ac.rs/fedora/get/o:7805/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dacić, Sanja A., 1973-. “Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova.” 2014. Web. 25 Feb 2021.

Vancouver:

Dacić, Sanja A. 1. Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova. [Internet] [Thesis]. Univerzitet u Beogradu; 2014. [cited 2021 Feb 25]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7805/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dacić, Sanja A. 1. Uticaj B vitaminskih kompleksa i ribavirina na odgovor nervnih i glijskih ćelija i oporavak motornih funkcija nakon povrede mozga pacova. [Thesis]. Univerzitet u Beogradu; 2014. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:7805/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manitoba

10. Dyck, Scott. Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury.

Degree: Physiology and Pathophysiology, 2015, University of Manitoba

URL: http://hdl.handle.net/1993/32952

► Populations of oligodendrocytes are susceptible to cell death following spinal cord injury (SCI), which results in axon demyelination. Multipotent resident neural precursor cells (NPCs) and… (more)

▼ Populations of oligodendrocytes are susceptible to cell death following spinal cord injury (SCI), which results in axon demyelination. Multipotent resident neural precursor cells (NPCs) and oligodendrocyte precursor cells (OPCs) have the innate potential to replace lost oligodendrocytes, however, their regenerative capabilities are limited within the milieu of SCI. Thus, development of therapies which promote endogenous oligodendrocyte replacement is a critical therapeutic target for SCI repair. Studies by our group have shown that upregulation of chondroitin sulfate proteoglycans (CSPGs) in the extracellular matrix appears to limit oligodendrocytes replacement after SCI. Importantly, it is known that targeting CSPGs can improve functional recovery after SCI. However, the cellular and molecular mechanisms underlying the inhibitory effects of CSPGs remain largely undefined. The discovery of CSPGs specific signaling receptors, leukocyte common antigen-related (LAR) and protein tyrosine phosphatase-sigma (PTPσ), allows us to uncover CSPGs direct mechanisms. Using in vitro models recapitulating the extracellular matrix of SCI, we first identify that CSPGs directly impede the ability of NPCs for proliferation and oligodendrocyte differentiation by signaling through LAR and PTPσ receptors and activation of the Rho/ROCK pathway. Pharmacological inhibition of LAR with Intracellular LAR peptide (ILP) and PTPσ with Intracellular Sigma peptide (ISP) is efficient to block nearly all CSPGs effect on NPCs in vitro. Similarly, the presence of CSPGs inhibits OPCs growth, maturation and myelination in vitro, which can be overcome by inhibition of LAR and PTPσ receptors. Capitalizing on these in vitro observation, we hypothesized that pharmacological blockage of LAR and PTPσ will promote endogenous oligodendrogenesis following SCI. Using a clinically relevant model of compressive/contusive SCI in the rat, we demonstrate that ILP and ISP play critical roles in regulating the endogenous cell response to injury. Perturbing LAR and PTPσ signaling attenuates oligodendrocyte apoptosis and myelin damage, while promoting oligodendrogenesis. We unraveled that LAR and PTPσ control oligodendrocyte differentiation partly by modulating microglia response and RhoA activity. In SCI, CSPGs contribute to the pro-inflammatory immune response by signaling through LAR and PTPσ, and that their inhibition forges a pro-regenerative inflammatory landscape characterized by interleukin-10 mediated mechanisms that fosters oligodendrocyte replacement and integrity. Thus, our findings uncover new roles for CSPGs in regulating secondary injury mechanisms in SCI. We have identified LAR and PTPσ as novel viable targets for modulating immune response and endogenous cell replacement following SCI. Advisors/Committee Members: Karimi, Soheila (Physiology and Pathophysiology) (supervisor), Eftekharpour, Eftekhar (Physiology and Pathophysiology) Werbowetski-Ogilvie, Tamra (Biochemistry and Medical Genetics) Hannila, Sari (Human Anatomy and Cell Science) Fouad, Karim (University of Alberta) (examiningcommittee).

Subjects/Keywords: Spinal cord injury; Glial scar; Astrogliosis; CSPGs; Chondroitin sulfate proteoglycans; Cell replacement; Oligodendrocyte replacement; Oligodendrogenesis; Neuroinflammation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Dyck, S. (2015). Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/32952

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Dyck, Scott. “Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury.” 2015. Thesis, University of Manitoba. Accessed February 25, 2021. http://hdl.handle.net/1993/32952.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Dyck, Scott. “Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury.” 2015. Web. 25 Feb 2021.

Vancouver:

Dyck S. Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury. [Internet] [Thesis]. University of Manitoba; 2015. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1993/32952.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Dyck S. Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury. [Thesis]. University of Manitoba; 2015. Available from: http://hdl.handle.net/1993/32952

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

11. Fuller, Molly Lynn. The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions.

Degree: PhD, Neurosciences, 2007, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

► The response of glial cells to injury of the adult central nervous system (CNS) leads to formation of a glial scar, a dense network of… (more)

▼ The response of glial cells to injury of the adult central nervous system (CNS) leads to formation of a glial scar, a dense network of astrocytes and extracellular matrix molecules. While the scar plays a protective role by creating a barrier between the CNS parenchyma and external environment, it is also one of the major factors leading to incomplete repair of tissue architecture and function. In this thesis, I examine the importance of bone morphogenetic proteins in glial cell reactivity after demyelinating injury. Using the model system of the dorsal columns of the rat thoracic spinal cord, I examined the acute behaviors of astrocytes and NG2+ glial precursors after LPC-induced demyelinating lesions. At three days after injection, levels of BMP4 and BMP7 are increased in the lesion, and the majority of cells contained phosphorylated Smad 1/5/8 in their nuclei. Expression of glial fibrillary acidic protein (GFAP) is increased in astrocytes at the lesion edge and expression of NG2 is increased on cells filling the core of the lesion. Vimentin is up-regulated in both of these populations. Cultures of mature astrocytes or NG2+ glial cells were treated with BMP4 or BMP7 and the quantity of chondroitin sulphate proteoglycans (CSPGs) were found to be increased at both the protein and RNA levels. Astrocytes doubled the mRNA levels for CSPG core proteins aggrecan and neurocan after one day of BMP treatment and displayed a maximum of 4-fold increase in CSPG protein after 4 days of treatment. NG2+ cells increased their aggrecan mRNA levels 14-fold and neurocan and versican levels 2-fold after 3 days of BMP4 treatment. BMP7 caused similar but smaller changes. These data link BMP signaling to glial scar formation after demyelination. The increase of CSPGs by BMPs is an event that is likely to inhibit migration of oligodendrocyte precursors and extension of regenerating neurites through the area of damage. Additionally, remyelination requires the recruitment of glial precursors and differentiation of those precursors into oligodendrocytes capable of myelination. Evidence of active BMP signaling in these cells, as shown here, would likely lead to the differentiation of precursors into astrocytes rather than oligodendrocytes. This work reveals BMPs as a possible therapeutic target for limiting glial scarring and optimizing the area of damage for remyelination. Advisors/Committee Members: Miller, Robert (Advisor).

Subjects/Keywords: Biology, Neuroscience; BMP; CSPG; glial scar; demyelination; CNS

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Fuller, M. L. (2007). The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

Chicago Manual of Style (16^th Edition):

Fuller, Molly Lynn. “The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions.” 2007. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed February 25, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990.

MLA Handbook (7^th Edition):

Fuller, Molly Lynn. “The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions.” 2007. Web. 25 Feb 2021.

Vancouver:

Fuller ML. The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2007. [cited 2021 Feb 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990.

Council of Science Editors:

Fuller ML. The Role of Bone Morphogenetic Proteins in Reactive Gliosis after Demyelinating Spinal Cord Lesions. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1183990990

NSYSU

12. Chen, Chun-Hong. The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury.

Degree: PhD, Doctoral Degree Program in Marine Biotechnology, 2016, NSYSU

URL: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730114-150126

► In the present study intrathecal pretreatment 11-dehydrosinulariolide attenuated spinal cord injury (SCI)-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins… (more)

▼ In the present study intrathecal pretreatment 11-dehydrosinulariolide attenuated spinal cord injury (SCI)-induced cell apoptosis by upregulating the antiapoptotic protein Bcl-2 and cell survival-related pathway proteins p-Akt and p-ERK, 8 h after SCI. Furthermore, the transcription factor p-CREB, which regulates Bcl-2 expression, was upregulated after 11-dehydrosinulariolide treatment. On day 7 after SCI, 11-dehydrosinulariolide exhibited an anti-inflammatory effect, attenuating SCI-induced upregulation of inducible NO synthase and tumor necrosis factor-Î±. 11-Dehydrosinulariolide also induced an increase in the expression of arginase-1 and CD206, markers of M2 microglia. Thus, the anti-inflammatory effect of 11-dehydrosinulariolide may be related to the promotion of an alternative pathway of microglia activation. On the basis of its neuroprotective and anti-inflammatory effects and ease of isolation from a coral that can be farmed, 11-dehydrosinulariolide is a potential neuroprotective agent. Besides of neuroprotection and anti-inflammation strategy, several studies suggest that glial scars pose as barriers that limit neurite regeneration after SCI. Evidences suggest that the activation of the PI3K/Akt/mTOR signaling pathway is involved in glial scar formation. In this study, we intrathecally injected a recombinant adenovirus carrying the pten gene to cause overexpression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in rats with SCI. Overexpression of PTEN following SCI attenuated gliosis, affected chondroitin sulfate proteoglycans expression, and improved axon regeneration into the lesion site led to improved locomotor function after SCI. Because delayed treatment with Ad-PTEN enhanced motor function recovery more significantly than immediate treatment with Ad-PTEN after SCI. These findings thus have positive implications for patients who are unable to receive immediate medical attention after SCI. Key words: marine natural product; 11-dehydrosinulariolide; microglia; neuroprotection; spinal cord injury; anti-inflammation; phosphatase and tensin homologue deleted on chromosome 10; astrocyte; glial scar; chondroitin sulfate proteoglycans. Advisors/Committee Members: Bin-Nan Wu (chair), Chien-Chih Chiu (chair), Chun-Sung Sung (chair), Zhi-Hong Wen (committee member), Wu-Fu Chen (chair), San-Nan Yang (chair), Ming-Hong Tai (chair).

Subjects/Keywords: microglia; marine natural product; 11-dehydrosinulariolide; neuroprotection; spinal cord injury; anti-inflammation; phosphatase and tensin homologue deleted on chromosome 10; astrocyte; glial scar; chondroitin sulfate proteoglycans

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, C. (2016). The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury. (Doctoral Dissertation). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730114-150126

Chicago Manual of Style (16^th Edition):

Chen, Chun-Hong. “The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury.” 2016. Doctoral Dissertation, NSYSU. Accessed February 25, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730114-150126.

MLA Handbook (7^th Edition):

Chen, Chun-Hong. “The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury.” 2016. Web. 25 Feb 2021.

Vancouver:

Chen C. The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury. [Internet] [Doctoral dissertation]. NSYSU; 2016. [cited 2021 Feb 25]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730114-150126.

Council of Science Editors:

Chen C. The therapeutic effects of coral-compound and PTEN in rats with traumatic spinal cord injury. [Doctoral Dissertation]. NSYSU; 2016. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0730114-150126

Duke University

13. Polikov, Vadim Steven. An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring .

Degree: 2009, Duke University

URL: http://hdl.handle.net/10161/3202

► Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis [1;2].… (more)

▼ Chronically implanted recording electrode arrays linked to prosthetics have the potential to make positive impacts on patients suffering from full or partial paralysis [1;2]. Such arrays are implanted into the patient's cortical tissue and record extracellular potentials from nearby neurons, allowing the information encoded by the neuronal discharges to control external devices. While such systems perform well during acute recordings, they often fail to function reliably in clinically relevant chronic settings [3]. Available evidence suggests that a major failure mode of electrode arrays is the brain tissue reaction against these implants (termed the glial scar), making the biocompatibility of implanted electrodes a primary concern in device design. Previous studies have focused on modifying the form factor of recording arrays, implanting such arrays in experimental animals, and, upon explantation, evaluating the glial scarring in response to the implant after several weeks in vivo. Because of a lack of information regarding the mechanisms involved in the tissue reaction to implanted biomaterials in the brain, it is not surprising that these in vivo studies have met with limited success. This dissertation describes the development of a simple, controlled in vitro model of glial scarring and the utilization of that model to probe the cellular and molecular mechanisms behind glial scarring. A novel in vitro model of glial scarring was developed by adapting a primary cell-based system previously used for studying neuroinflammatory processes in neurodegenerative disease [4]. Midbrains from embryonic day 14 Fischer 344 rats were mechanically dissociated and grown on poly-D-lysine coated 24 well plates to a confluent layer of neurons, astrocytes, and microglia. The culture was injured with either a mechanical scrape or foreign-body placement (segments of 50 mm diameter stainless steel microwire), fixed at time points from 6 h to 10 days, and assessed by immunocytochemistry. Microglia invaded the scraped wound area at early time points and hypertrophied activated astrocytes repopulated the wound after 7 days. The chronic presence of microwire resulted in a glial scar forming at 10 days, with microglia forming an inner layer of cells coating the microwire, while astrocytes surrounded the microglial core with a network of cellular processes containing upregulated GFAP. Neurons within the culture did not repopulate the scrape wound and did not respond to the microwire, although they were determined to be electrically active through patch clamp recording. This initial model recreated many of the hallmarks of glial scarring around electrodes used for recording in the brain; however, the model lacked the reproducibility necessary to establish a useful characterization tool. After the protocol was amended to resemble protocols typically used to culture neural stem/precursor cells, an intense scarring reaction was consistently seen [5]. To further optimize and characterize the reaction, six independent cell culture… Advisors/Committee Members: Reichert, William "Monty" (advisor).

Subjects/Keywords: Biomedical Engineering; Neurosciences; astrocyte; cortical electrodes; glial scar; in vitro; neural precursor cell

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Polikov, V. S. (2009). An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring . (Thesis). Duke University. Retrieved from http://hdl.handle.net/10161/3202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Polikov, Vadim Steven. “An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring .” 2009. Thesis, Duke University. Accessed February 25, 2021. http://hdl.handle.net/10161/3202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Polikov, Vadim Steven. “An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring .” 2009. Web. 25 Feb 2021.

Vancouver:

Polikov VS. An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring . [Internet] [Thesis]. Duke University; 2009. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10161/3202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Polikov VS. An in vitro model of the brain tissue reaction to chronically implanted recording electrodes reveals essential roles for serum and bFGF in glial scarring . [Thesis]. Duke University; 2009. Available from: http://hdl.handle.net/10161/3202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Arkansas

14. Walker, Addison. Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury.

Degree: MSBME, 2016, University of Arkansas

URL: https://scholarworks.uark.edu/etd/1754

► Following injury to the central nervous system, extracellular modulations are apparent at the site of injury, often resulting in a glial scar. Astrocytes are… (more)

Subjects/Keywords: Biological sciences; Applied sciences; Astrocytes; Extracellular matrix; Glial scar; Repeat injury; Traumatic brain injury; Bioelectrical and Neuroengineering; Cell Biology; Molecular and Cellular Neuroscience

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APA (6^th Edition):

Walker, A. (2016). Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury. (Masters Thesis). University of Arkansas. Retrieved from https://scholarworks.uark.edu/etd/1754

Chicago Manual of Style (16^th Edition):

Walker, Addison. “Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury.” 2016. Masters Thesis, University of Arkansas. Accessed February 25, 2021. https://scholarworks.uark.edu/etd/1754.

MLA Handbook (7^th Edition):

Walker, Addison. “Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury.” 2016. Web. 25 Feb 2021.

Vancouver:

Walker A. Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury. [Internet] [Masters thesis]. University of Arkansas; 2016. [cited 2021 Feb 25]. Available from: https://scholarworks.uark.edu/etd/1754.

Council of Science Editors:

Walker A. Exploring the Production of Extracellular Matrix by Astrocytes in Response to Mimetic Traumatic Brain Injury. [Masters Thesis]. University of Arkansas; 2016. Available from: https://scholarworks.uark.edu/etd/1754

15. Hagerty, Kailyn M. Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke.

Degree: MS, Physiology and Neuroscience, 2012, Wright State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=wright1341957043

► Stroke is one of the leading causes of death and the top cause of long term disability. Currently there exists no standardized treatment of care… (more)

Subjects/Keywords: Neurosciences; ischemic stroke; rats; fluoxetine; angiogenesis; glial scar

…infarct (indicative of a glial scar) or spread out 24 and in diffuse areas away… …These animals were used to compare differences in angiogenesis, glial scarring, and infarct… …oxide synthase (eNOS, 5 μg/mL, AbCAM antibody) and glial fibrillary acidic protein…

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APA (6^th Edition):

Hagerty, K. M. (2012). Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke. (Masters Thesis). Wright State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=wright1341957043

Chicago Manual of Style (16^th Edition):

Hagerty, Kailyn M. “Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke.” 2012. Masters Thesis, Wright State University. Accessed February 25, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=wright1341957043.

MLA Handbook (7^th Edition):

Hagerty, Kailyn M. “Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke.” 2012. Web. 25 Feb 2021.

Vancouver:

Hagerty KM. Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke. [Internet] [Masters thesis]. Wright State University; 2012. [cited 2021 Feb 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1341957043.

Council of Science Editors:

Hagerty KM. Comparing Two Different Statins in a Delayed Pharmacological Treatment for Ischemic Stroke. [Masters Thesis]. Wright State University; 2012. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=wright1341957043

16. Thomaty, Sandie. Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat.

Degree: Docteur es, Neurosciences, 2015, Aix Marseille Université

URL: http://www.theses.fr/2015AIXM4772

►

Les lésions spinales conduisent à des altérations majeures des fonctions sensorimotrices. Les récupérations fonctionnelles consécutives à ces atteintes sont très limitées, notamment en raison des… (more)

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Les lésions spinales conduisent à des altérations majeures des fonctions sensorimotrices. Les récupérations fonctionnelles consécutives à ces atteintes sont très limitées, notamment en raison des capacités réduites de réparation des tissus endommagés dans le SNC. En outre, ces récupérations dépendent notamment de plusieurs processus cellulaires tels que l'activation astrogliale qui conduit à la formation de la cicatrice gliale, ou encore l'inflammation dont les cellules microgliales et les mastocytes sont les effecteurs les plus précoces. Cette inflammation est connue pour exacerber les dommages tissulaires et restreindre les possibilités de récupération. Cependant, des études récentes chez l'animal et chez l'Homme montrent que l'inflammation pourrait également avoir des effets favorisant les processus de récupération. Le but de cette thèse était de mieux comprendre les liens qui existent entre neuroinflammation, neuroplasticité et récupérations fonctionnelles après lésion spinale. L’objectif expérimental visait à examiner les réactivités microgliales, mastocytaires et astrocytaires post-lésionnelles, en parallèle avec des restaurations fonctionnelles. Dans ce contexte nous nous sommes plus particulièrement intéressés à l'influence d'une cytokine pro-inflammatoire, le Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) sur ces processus inflammatoires et la plasticité fonctionnelle après une hémisection C4-C5 chez le rat adulte. L’ensemble de nos travaux suggère que le GM-CSF pourrait agir par l’intermédiaire de plusieurs événements cellulaires et moléculaires, en favorisant des phénomènes de plasticité adaptatifs et la récupération partielle de fonctions altérées.

Spinal cord injuries are mostly of traumatic origin and result in major sensorimotor deficits. Postlesion functional recovery is limited, especially because of the reduced capacity of repairing damaged tissues. Moreover, this recovery depends specifically on several cellular processes such as astroglial activation conducting to glial scar formation, or inflammation for which microglial and mast cells are the earliest effectors. This inflammation is known to exacerbate tissue damages and restrain the capacity to recover. However, recent studies in animals and humans show that inflammation may also have beneficial aeffects on recovery processes. The studies conducted during my doctoral research were intended to better understand the links between neuroinflammation, neuroplasticity and functional recovery following spinal cord injury. We aimed at examining microglial, mast cells and astroglial reactivities after the injury, in relation with functional recovery of somatosensory and motor functions. In this context, we were particularly interested in the influence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) on inflammatory and plasticity mechanisms after a C4-C5 hemisection in the adult rat. Our doctoral research suggests that GM-CSF could act through several cellular and molecular events promoting adaptive plasticity phenomena…

Advisors/Committee Members: Xerri, Christian (thesis director), Brezun, Jean-Michel (thesis director).

Subjects/Keywords: Gm-Csf; Neuroinflammation; Neuroplasticité; Microglie; Mastocytes; Cicatrice gliale; Lésion spinale; Récupérations fonctionnelles; Réorganisations corticales; Rat adulte; Gm-Csf; Neuroinflammation; Neuroplasticity; Microglia; Mast cells; Glial scar; Spinal cord injury; Functional recovery; Cortical reorganization; Adult rat

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Thomaty, S. (2015). Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat. (Doctoral Dissertation). Aix Marseille Université. Retrieved from http://www.theses.fr/2015AIXM4772

Chicago Manual of Style (16^th Edition):

Thomaty, Sandie. “Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat.” 2015. Doctoral Dissertation, Aix Marseille Université. Accessed February 25, 2021. http://www.theses.fr/2015AIXM4772.

MLA Handbook (7^th Edition):

Thomaty, Sandie. “Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat.” 2015. Web. 25 Feb 2021.

Vancouver:

Thomaty S. Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat. [Internet] [Doctoral dissertation]. Aix Marseille Université 2015. [cited 2021 Feb 25]. Available from: http://www.theses.fr/2015AIXM4772.

Council of Science Editors:

Thomaty S. Influence des processus inflammatoires sur la neuroplasticité et sur les récupérations fonctionnelles après lésion spinale chez le rat adulte : Influence of inflammatory processes on neuroplasticity and functional recovery after spinal cord injury in the adult rat. [Doctoral Dissertation]. Aix Marseille Université 2015. Available from: http://www.theses.fr/2015AIXM4772

17. Manns, Richard Peter Charles. Repulsive cues and signalling cascades of the axon growth cone.

Degree: PhD, 2013, University of Cambridge

URL: https://www.repository.cam.ac.uk/handle/1810/245741https://www.repository.cam.ac.uk/bitstream/1810/245741/10/thesis.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/245741/11/thesis.pdf.jpg

► The aim of the work described in this thesis is to investigate the nature and mechanisms of action of repellent cues for growing axons. In… (more)

▼ The aim of the work described in this thesis is to investigate the nature and mechanisms of action of repellent cues for growing axons. In particular I try to resolve the controversy in the literature regarding the need for protein synthesis in the growth cone in response to external guidance cues. My results resolve the conflicting data in the literature on Semaphorin-3A signalling, where differing labs had shown that inhibiting protein synthesis either blocks or has no effect upon repulsion. They demonstrate the presence of at least two independent pathways, protein synthesisdependent mTOR activation and -independent GSK3β activation. The higher sensitivity of the synthesis-dependent pathway, and its redundancy at higher concentrations where synthesisindependent mechanisms can evoke a full collapse response alone, resolve the apparent conflict. My experiments also demonstrated that Nogo-δ20, a domain of Nogo-A, requires local protein synthesis to cause collapse. Unlike Semaphorin-3A, the dependence of collapse upon protein synthesis is concentration-independent and does not involve guanylyl cyclase, but it does share a dependence upon mTOR activity and the synthesis of RhoA, sufficient to cause collapse downstream of Semaphorin-3A. The other axon-repelling domain of Nogo-A, Nogo-66, is partially dependent upon the proteasome instead. It does not share a common pathway with Nogo-δ20, except that both are RhoA-dependent. I further attempted to identify the nature of a repulsive activity found in grey matter, ruling out a previously suggested candidate identity. Finally, I examined the phenomenon of nitric oxide-induced growth cone collapse. My experiments revealed that S-nitrosylated glutathione causes growth cone collapse through the activity of protein disulphide isomerase. This mechanism shows only a partial dependence upon soluble guanylyl cyclase, but I argue that it has total dependence upon an S-nitrosylated donor. Coupled with its apparent relation to Spalmitoylation, the reciprocal of S-nitrosylation, I propose that nitric oxide causes collapse by crossing the cell membrane to inhibit S-palmitoylation–determined localisation of proteins. These results reveal some of the many pathways involved in growth cone collapse, whose further characterisation may provide new targets for the treatment of injuries of the central nervous system.

Subjects/Keywords: axon repulsion; axon guidance; neuron; glial scar; astrocyte; gliosis; spinal cord; prosaposin; nitrosylation; dorsal root ganglion; Semaphorin-3A; astroglioma; rapamycin; mTOR; Nogo-66; amino-Nogo; Nogo-A; reticulon-4A; nitric oxide; cGMP; proteasome; concentration dependence; growth cone; quantitative immunofluorescence; protein disulphide isomerase; protein disulfide isomerase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Manns, R. P. C. (2013). Repulsive cues and signalling cascades of the axon growth cone. (Doctoral Dissertation). University of Cambridge. Retrieved from https://www.repository.cam.ac.uk/handle/1810/245741https://www.repository.cam.ac.uk/bitstream/1810/245741/10/thesis.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/245741/11/thesis.pdf.jpg

Chicago Manual of Style (16^th Edition):

Manns, Richard Peter Charles. “Repulsive cues and signalling cascades of the axon growth cone.” 2013. Doctoral Dissertation, University of Cambridge. Accessed February 25, 2021. https://www.repository.cam.ac.uk/handle/1810/245741https://www.repository.cam.ac.uk/bitstream/1810/245741/10/thesis.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/245741/11/thesis.pdf.jpg.

MLA Handbook (7^th Edition):

Manns, Richard Peter Charles. “Repulsive cues and signalling cascades of the axon growth cone.” 2013. Web. 25 Feb 2021.

Vancouver:

Manns RPC. Repulsive cues and signalling cascades of the axon growth cone. [Internet] [Doctoral dissertation]. University of Cambridge; 2013. [cited 2021 Feb 25]. Available from: https://www.repository.cam.ac.uk/handle/1810/245741https://www.repository.cam.ac.uk/bitstream/1810/245741/10/thesis.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/245741/11/thesis.pdf.jpg.

Council of Science Editors:

Manns RPC. Repulsive cues and signalling cascades of the axon growth cone. [Doctoral Dissertation]. University of Cambridge; 2013. Available from: https://www.repository.cam.ac.uk/handle/1810/245741https://www.repository.cam.ac.uk/bitstream/1810/245741/10/thesis.pdf.txt ; https://www.repository.cam.ac.uk/bitstream/1810/245741/11/thesis.pdf.jpg

18. Alizadeh, Arsalan. Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury.

Degree: Physiology and Pathophysiology, 2018, University of Manitoba

URL: http://hdl.handle.net/1993/33364

► Spinal cord injury (SCI) elicits a robust glial and neuroinflammatory response that governs secondary injury processes and causes progressive neural degeneration and loss of neurological… (more)

▼ Spinal cord injury (SCI) elicits a robust glial and neuroinflammatory response that governs secondary injury processes and causes progressive neural degeneration and loss of neurological function. Activated glial and immune cells produce a plethora of inhibitory and toxic mediators that lay the foundation for a non-permissive microenvironment for neural repair and regeneration. Resident astrocytes and microglia together with blood-borne monocytes, T cells and B cells are the main orchestrators of secondary injury processes following SCI. Despite detrimental effects, these cells possess the ability to play pro-regenerative roles in response to proper modulatory signals from their microenvironment. Hence, identifying new therapeutic targets to promote the supportive aspect of glial and immune response is a viable approach for the treatment of SCI. To develop such targeted therapies, it is necessary to understand the endogenous mechanisms that regulate astrogliosis and neuroinflammation following SCI. Our team has previously discovered an acute and sustained depletion in spinal cord tissue levels of the neuronally derived Neuregulin-1 (Nrg-1) following SCI. Further studies by our group established a correlation between the injury-induced depletion of Nrg-1 and the inadequate oligodendrocyte replacement after SCI. Similar to oligodendrocytes, glial and immune cells also express Nrg-1 receptors, ErbB2, 3, 4, suggesting potential ramifications of Nrg-1 dysregulation on glial activity and neuroinflammation. Recent studies have also identified an immunomodulatory role for Nrg-1 in ischemic brain injuries. Based on this body of evidence, we hypothesized that diminished tissue levels of Nrg-1 in the injured spinal cord contribute to the imbalanced glial and immune response following SCI. Using an in vitro model of activated astrocytes and microglia and a clinically relevant in vivo model of rat compressive-contusive SCI, we unravel the role of Nrg-1 in regulating II astrogliosis and immune response following SCI. We show for the first time that Nrg-1 treatment moderates several detrimental characteristic aspects of activated glia such as chondroitin sulfate proteoglycans (CSPGs), nitric oxide (NO) and pro-inflammatory cytokine production. Mechanistically, we demonstrate that Nrg-1 effects on activated glia are mediated through an ErbB2/3 heterodimer complex and activation of Erk1/2 and STAT3 pathways. In SCI, our comprehensive analysis of immune and glial response using Western blotting, qPCR, immunohistochemistry and flow cytometry shows that Nrg-1 treatment reduces glial scar formation and induces a pro-regenerative regulatory phenotype in T and B cells and macrophages in the spinal cord and peripheral blood during the acute and chronic stages of SCI. Nrg-1 fosters a more balanced post-SCI microenvironment by attenuating antibody deposition and expression of pro-inflammatory cytokines and chemokines such as IL-6, IL-1β and TNF-⍺ while upregulating pro-regenerative mediators such as arginase-1, CCL11 and IL-10. Moreover,… Advisors/Committee Members: Karimi-Abdolrezaee, Soheila (Physiology and Pathophysiology) (supervisor), Gardiner, Phillip (Physiology and Pathophysiology) Anderson, Christopher (Pharmacology and Therapeutics) Fernyhough, Paul (Pharmacology and Therapeutics) Yong, Voon Wee (University of Calgary) (examiningcommittee).

Subjects/Keywords: Spinal Cord Injury; Glial Scar; Neuroinflammation; Neuregulin-1; T cells; B cells; Macrophages; Microglia; Astrocytes

…B Lymphocytes 27 1.2.2.6 Glial Scar Formation 33 1.3 Neuregulin-1 40 1.3.1… …Neuroinflammation and glial scar formation in SCI. 38 Figure 1.5 Structural diversity of Nrg-1. 42… …activation Demyelination Glial scar formation Oligodendrocyte loss Fig. 1.2: Secondary injury… …lead to progressive neural tissue damage. Glial cell activation, scar formation and… …Objectives 59 1.5 References 61 Chapter 2: Neuregulin-1 Positively Modulates Glial Response and…

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Alizadeh, A. (2018). Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury. (Thesis). University of Manitoba. Retrieved from http://hdl.handle.net/1993/33364

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Alizadeh, Arsalan. “Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury.” 2018. Thesis, University of Manitoba. Accessed February 25, 2021. http://hdl.handle.net/1993/33364.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Alizadeh, Arsalan. “Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury.” 2018. Web. 25 Feb 2021.

Vancouver:

Alizadeh A. Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury. [Internet] [Thesis]. University of Manitoba; 2018. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1993/33364.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Alizadeh A. Elucidating the role of neuregulin-1 in glial and immune response following traumatic spinal cord injury. [Thesis]. University of Manitoba; 2018. Available from: http://hdl.handle.net/1993/33364

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Cambridge

19. Manns, Richard Peter Charles. Repulsive cues and signalling cascades of the axon growth cone.

Degree: PhD, 2013, University of Cambridge

URL: https://doi.org/10.17863/CAM.16341 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607707

► The aim of the work described in this thesis is to investigate the nature and mechanisms of action of repellent cues for growing axons. In… (more)

▼ The aim of the work described in this thesis is to investigate the nature and mechanisms of action of repellent cues for growing axons. In particular I try to resolve the controversy in the literature regarding the need for protein synthesis in the growth cone in response to external guidance cues. My results resolve the conflicting data in the literature on Semaphorin-3A signalling, where differing labs had shown that inhibiting protein synthesis either blocks or has no effect upon repulsion. They demonstrate the presence of at least two independent pathways, protein synthesis-dependent mTOR activation and -independent GSK3? activation. The higher sensitivity of the synthesis-dependent pathway, and its redundancy at higher concentrations where synthesis-independent mechanisms can evoke a full collapse response alone, resolve the apparent conflict. My experiments also demonstrated that Nogo-?20, a domain of Nogo-A, requires local protein synthesis to cause collapse. Unlike Semaphorin-3A, the dependence of collapse upon protein synthesis is concentration-independent and does not involve guanylyl cyclase, but it does share a dependence upon mTOR activity and the synthesis of RhoA, sufficient to cause collapse downstream of Semaphorin-3A. The other axon-repelling domain of Nogo-A, Nogo-66, is partially dependent upon the proteasome instead. It does not share a common pathway with Nogo-?20, except that both are RhoA-dependent. I further attempted to identify the nature of a repulsive activity found in grey matter, ruling out a previously suggested candidate identity. Finally, I examined the phenomenon of nitric oxide-induced growth cone collapse. My experiments revealed that S-nitrosylated glutathione causes growth cone collapse through the activity of protein disulphide isomerase. This mechanism shows only a partial dependence upon soluble guanylyl cyclase, but I argue that it has total dependence upon an S-nitrosylated donor. Coupled with its apparent relation to S-palmitoylation, the reciprocal of S-nitrosylation, I propose that nitric oxide causes collapse by crossing the cell membrane to inhibit S-palmitoylation-determined localisation of proteins. These results reveal some of the many pathways involved in growth cone collapse, whose further characterisation may provide new targets for the treatment of injuries of the central nervous system.

Subjects/Keywords: 612.8; axon repulsion; axon guidance; neuron; glial scar; astrocyte; gliosis; spinal cord; prosaposin; nitrosylation; dorsal root ganglion; Semaphorin-3A; astroglioma; rapamycin; mTOR; Nogo-66; amino-Nogo; Nogo-A; reticulon-4A; nitric oxide; cGMP; proteasome; concentration dependence; growth cone; quantitative immunofluorescence; protein disulphide isomerase; protein disulfide isomerase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Manns, R. P. C. (2013). Repulsive cues and signalling cascades of the axon growth cone. (Doctoral Dissertation). University of Cambridge. Retrieved from https://doi.org/10.17863/CAM.16341 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607707

Chicago Manual of Style (16^th Edition):

Manns, Richard Peter Charles. “Repulsive cues and signalling cascades of the axon growth cone.” 2013. Doctoral Dissertation, University of Cambridge. Accessed February 25, 2021. https://doi.org/10.17863/CAM.16341 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607707.

MLA Handbook (7^th Edition):

Manns, Richard Peter Charles. “Repulsive cues and signalling cascades of the axon growth cone.” 2013. Web. 25 Feb 2021.

Vancouver:

Manns RPC. Repulsive cues and signalling cascades of the axon growth cone. [Internet] [Doctoral dissertation]. University of Cambridge; 2013. [cited 2021 Feb 25]. Available from: https://doi.org/10.17863/CAM.16341 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607707.

Council of Science Editors:

Manns RPC. Repulsive cues and signalling cascades of the axon growth cone. [Doctoral Dissertation]. University of Cambridge; 2013. Available from: https://doi.org/10.17863/CAM.16341 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607707

20. Pillet, Laure-Elise. Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model.

Degree: Docteur es, Neurobiologie, 2018, Sorbonne Paris Cité

URL: http://www.theses.fr/2018USPCB246

►

La synapse est le lieu de communication entre les neurones à l'origine de nos capacités cognitives. Les mutations des gènes codant pour des protéines synaptiques… (more)

▼

La synapse est le lieu de communication entre les neurones à l'origine de nos capacités cognitives. Les mutations des gènes codant pour des protéines synaptiques sont responsables des maladies neurodéveloppementales appelées synaptopathies, recouvrant un large spectre de pathologies, de la déficience intellectuelle aux troubles du spectre autistique. Cependant, il est actuellement établi que les neurones ne sont pas les seuls acteurs au niveau de la synapse. Les astrocytes jouent également un rôle essentiel dans la mise en place du réseau neuronal et le fonctionnement de la synapse. Ils assurent aussi l'homéostasie ionique synaptique et sont capables de sécréter des glio-transmetteurs qui modulent l'activité synaptique. Oligophrénine-1 (OPHN1) est un gène associé à la déficience intellectuelle liée à l'X chez l'Homme. OPHN1 est une protéine synaptique dont les fonctions neuronales sont bien connues. La protéine peut directement interagir avec le cytosquelette d'actine et joue un rôle dans la formation et la maturation des épines dendritiques. Cette protéine est aussi exprimée dans les astrocytes mais sa fonction astrocytaire n'est pas connue. A l'aide d'un modèle KO de souris pour Ophn1, nous avons mis en évidence les conséquences de l'absence d'Ophn1 dans les astrocytes. Nous avons démontré que la délétion d'OPHN1 altère la migration et la morphologie des astrocytes in vitro. Sachant qu'Ophn1 est capable d'inactiver la GTPase RhoA, nous avons utilisé un inhibiteur de la voie RhoA/ROCK pour retrouver un phénotype de migration normal. In vivo nous avons choisi un modèle de cicatrisation gliale cortical afin de pouvoir observer la migration et la morphologie des astrocytes au niveau de la cicatrice. Nous avons observé que la délétion d'Ophn1 altérait la cicatrisation gliale et que les astrocytes à proximité de la cicatrice était moins ramifiés. L'ensemble de ces résultats nous permet de constater que les astrocytes sont altérés dans notre modèle murin de déficience intellectuelle liée à l'X. De plus, le KO conditionel astrocytaire mis en place nous permettra à l'avenir d'étudier les conséquences de la perte d'OPHN1 uniquement dans les astrocytes, et de comprendre la contribution astrocytaire dans la physiopathologie de cette maladie neuro-développementale.

The synapse mediates the inter-neuron communication that forms the basis of all cognitive activity. Mutations in genes encoding for synaptic proteins are responsible for neurodevelopmental disorders called synaptopathies, covering a large clinical spectrum from intellectual disability (ID) to autism spectrum disorders. However it is currently established that neurons are not the only active cells at the synapse. Astrocytes play as well an essential role for its development and functioning. They maintain synaptic ionic homeostasis and are capable of secreting gliotransmitters, which can modulate synaptic activity. Oligophrenin-1 gene (OPHN1) was identified and associated with X-linked human ID. OPHN1 is a synaptic protein, which neuronal function is well known. It…

Advisors/Committee Members: Billuart, Pierre (thesis director), Rouach-Holcman, Nathalie (thesis director).

Subjects/Keywords: Déficience intellectuelle; Oligophrénine-1; RhoGAP; Myosin light chain; Astrocytes; Cicarisation gliale corticale; Migration; Morphologie; KO conditionnel astrocytaire; Intellectual disability; Oligophrenin-1; RhoGAP; Myosin light chain; Astrocytes; Cotical glial scar; Migration; Morphology; Astrocytic conditional KO; 616.858 8

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pillet, L. (2018). Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model. (Doctoral Dissertation). Sorbonne Paris Cité. Retrieved from http://www.theses.fr/2018USPCB246

Chicago Manual of Style (16^th Edition):

Pillet, Laure-Elise. “Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model.” 2018. Doctoral Dissertation, Sorbonne Paris Cité. Accessed February 25, 2021. http://www.theses.fr/2018USPCB246.

MLA Handbook (7^th Edition):

Pillet, Laure-Elise. “Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model.” 2018. Web. 25 Feb 2021.

Vancouver:

Pillet L. Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model. [Internet] [Doctoral dissertation]. Sorbonne Paris Cité; 2018. [cited 2021 Feb 25]. Available from: http://www.theses.fr/2018USPCB246.

Council of Science Editors:

Pillet L. Interactions neurogliales dans la déficience intellectuelle : étude du modèle oligophrénine-1 : Astroglial contribution to synaptophaties : the oligophrenin1 gene model. [Doctoral Dissertation]. Sorbonne Paris Cité; 2018. Available from: http://www.theses.fr/2018USPCB246

Georgia Tech

21. McConnell, George Charles. Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state.

Degree: PhD, Biomedical Engineering, 2008, Georgia Tech

URL: http://hdl.handle.net/1853/26615

► Thanks to pioneering scientists and clinicians, prosthetic devices that are controlled by intra-cortical electrodes recording one's 'thoughts' are a reality today, and no longer merely… (more)

▼ Thanks to pioneering scientists and clinicians, prosthetic devices that are controlled by intra-cortical electrodes recording one's 'thoughts' are a reality today, and no longer merely in the realm of science fiction. However, widespread clinical use of implanted electrodes is hampered by a lack of reliability in chronic recordings, independent of the type of electrodes used. The dominant hypothesis has been that astroglial scar electrically impedes the electrodes. However, recent studies suggest that the impedance changes associated with the astroglial scar are not high enough to interfere significantly impair neural recordings. Furthermore, there is a time delay between when scar electrically stabilizes and when neural recordings fail (typically >1 month lag), suggesting that scar, per se, does not cause chronic recording unreliability. In this study, an alternative hypothesis was tested in a rat model, namely, that chronic inflammation surrounding microelectrodes causes a local neurodegenerative state. Chronic inflammation was varied in three ways: 1) stab wound control, 2) age-matched control, and 3) inter-shank spacing of a multishank electrode. The results of this study suggest that chronic inflammation, as indicated by activated microglia and reactive astrocytes, is correlated with local neurodegeneration, marked by neuron cell death and dendritic loss. Surprisingly, axonal pathology in the form of hyperphosphorylation of the protein Tau (the hallmark of many tauopathies, including Alzheimer's Disease) was also observed in the immediate vicinity of microelectrodes implanted for 16 weeks. Additionally, work is presented on a fast, non-invasive method to monitor the astrocytic response to intra-cortical electrodes using electrical impedance spectroscopy. This work provides a non-invasive monitoring tool for inflammation, albeit an indirect one, and fills a gap which has slowed the development of strategies to control the inflammatory tissue response surrounding microelectrodes and thereby improve the reliability of chronic neural recordings. The results of these experiments have significance for the field of neuroengineering, because a more accurate understanding of why recordings fail is integral to engineering reliable solutions for integrating brain tissue with microelectrode arrays. Advisors/Committee Members: Bellamkonda, Ravi (Committee Chair), Babensee, Julia (Committee Member), Butera, Robert (Committee Member), DeWeerth, Steve (Committee Member), Lee, Robert (Committee Member), McKeon, Robert (Committee Member).

Subjects/Keywords: Immunohistochemistry; Neural recording; Chronic implants; Brain; Silicon; Impedance spectroscopy; Neurodegeneration; Neuroinflammation; Laminin; Neuroprosthesis; Microelectrode; Cole; Bioimpedance; Biosensor; Astroglial scar; Biocompatibility; Glial scar; Implants, Artificial; Microelectrode; Foreign-body reaction; Inflammation

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APA (6^th Edition):

McConnell, G. C. (2008). Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/26615

Chicago Manual of Style (16^th Edition):

McConnell, George Charles. “Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state.” 2008. Doctoral Dissertation, Georgia Tech. Accessed February 25, 2021. http://hdl.handle.net/1853/26615.

MLA Handbook (7^th Edition):

McConnell, George Charles. “Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state.” 2008. Web. 25 Feb 2021.

Vancouver:

McConnell GC. Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state. [Internet] [Doctoral dissertation]. Georgia Tech; 2008. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1853/26615.

Council of Science Editors:

McConnell GC. Chronic inflammation surrounding intra-cortical electrodes is correlated with a local, neurodegenerative state. [Doctoral Dissertation]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/26615

Georgia Tech

22. Zhong, Yinghui. Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes.

Degree: PhD, Biomedical Engineering, 2006, Georgia Tech

URL: http://hdl.handle.net/1853/19760

► Stable single-unit recordings from the nervous system using microelectrode arrays can have significant implications for the treatment of a wide variety of sensory and movement… (more)

Subjects/Keywords: Neural implant; Drug delivery; Coatings; Inflammation; Glial scar; Nervous system; Electrodes; Implants, Artificial; Foreign-body reaction; Wound healing; Neuroglia; Coatings; Controlled release preparations; Anti-inflammatory agents

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APA (6^th Edition):

Zhong, Y. (2006). Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/19760

Chicago Manual of Style (16^th Edition):

Zhong, Yinghui. “Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes.” 2006. Doctoral Dissertation, Georgia Tech. Accessed February 25, 2021. http://hdl.handle.net/1853/19760.

MLA Handbook (7^th Edition):

Zhong, Yinghui. “Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes.” 2006. Web. 25 Feb 2021.

Vancouver:

Zhong Y. Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes. [Internet] [Doctoral dissertation]. Georgia Tech; 2006. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1853/19760.

Council of Science Editors:

Zhong Y. Development and Characterization of Anti-Inflammatory Coatings for Implanted Neural Probes. [Doctoral Dissertation]. Georgia Tech; 2006. Available from: http://hdl.handle.net/1853/19760

23. Millner, Mary Angela. Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration.

Degree: MS, Biomedical Engineering, 2008, Georgia Tech

URL: http://hdl.handle.net/1853/24647

► Injury to the central nervous system (CNS) results in the formation of a highly inhibitory glial scar consisting mainly of chondroitin sulfate proteoglycans (CSPGs). CSPGs… (more)

▼ Injury to the central nervous system (CNS) results in the formation of a highly inhibitory glial scar consisting mainly of chondroitin sulfate proteoglycans (CSPGs). CSPGs are comprised of a protein core with covalently attached chondroitin sulfate glycosaminoglycan (CS-GAG) side chains. CSPGs and CS-GAGs have been implicated in the regenerative failure of the CNS, though the mechanism underlying inhibition is unclear. Sulfation affects both the physical and chemical characteristics of CS-GAGs and, therefore, it has been hypothesized that certain sulfation patterns are more inhibitory than others. To investigate this hypothesis, specific chondroitin sulfate sulfotransferases (CSSTs), the enzymes responsible for CS-GAG sulfation, were knocked down in vitro using siRNA. C4ST-1, C4ST-2, and C46ST were chosen as targets for gene knockdown in this study based on their expression in neural tissue and the extent of inhibition caused by their respective CS-GAG. It was hypothesized that transfection of primary rat astrocytes with siRNAs designed to prevent the expression of C4ST-1, C4ST-2, and C46ST would decrease specific sulfation patterns of CSPGs, resulting in improved neurite extension in a neurite guidance assay. Through optimization of siRNA dose, astrocyte viability was maintained while successfully knocking down mRNA levels of C4ST-1, C4ST-2, and C46ST and significantly reducing total levels of secreted CS-GAGs. However, no increase in the incidence of neurite extension was observed using conditioned media collected from siRNA transfected astrocytes compared to non-transfected controls. These data suggest that sulfation does not contribute to CSPG-mediated neurite inhibition, though further investigation is necessary to confirm these findings. Significantly, this work has established a paradigm for investigating the role of CSPG sulfation patterns in CNS regeneration. Advisors/Committee Members: Bellamkonda, Ravi (Committee Chair), LaPlaca, Michelle (Committee Member), McKeon, Robert (Committee Member).

Subjects/Keywords: Nerve regeneration; Glycosaminoglycan; Chondroitin sulfate; Astrocyte; Glial scar; Central nervous system wounds and injuries.; Chondroitin sulfates; Proteoglycans

…CNS) results in the formation of a highly inhibitory glial scar consisting mainly of… …inhibitory glial scar, which presents both biochemical and physical barriers. Disruption of the… …recovery after injury. Hence, the glial scar acts as both a physical and chemical barrier to… …forming the highly inhibitory glial scar. CSPGs often function through their interactions with… …injured spinal cord must overcome the inhibitory effects of the glial scar while maintaining its…

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APA (6^th Edition):

Millner, M. A. (2008). Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration. (Masters Thesis). Georgia Tech. Retrieved from http://hdl.handle.net/1853/24647

Chicago Manual of Style (16^th Edition):

Millner, Mary Angela. “Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration.” 2008. Masters Thesis, Georgia Tech. Accessed February 25, 2021. http://hdl.handle.net/1853/24647.

MLA Handbook (7^th Edition):

Millner, Mary Angela. “Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration.” 2008. Web. 25 Feb 2021.

Vancouver:

Millner MA. Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration. [Internet] [Masters thesis]. Georgia Tech; 2008. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/1853/24647.

Council of Science Editors:

Millner MA. Modulation of CSPG sulfation patterns through siRNA silencing of sulfotransferase expression to promote CNS regeneration. [Masters Thesis]. Georgia Tech; 2008. Available from: http://hdl.handle.net/1853/24647

24. Filous, Angela R, Ph.D. The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury.

Degree: PhD, Neurosciences, 2014, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1396605992

► Macrophage infiltration into the lesion core after spinal cord injury causes injured dystrophic axons to dieback from the lesion center. Although it was once thought… (more)

▼ Macrophage infiltration into the lesion core after spinal cord injury causes injured dystrophic axons to dieback from the lesion center. Although it was once thought these fibers would retract until they reached a collateral, previous work from our laboratory showed that injured sensory axons actually stabilize just caudal to the lesion on a population of cells that express high amounts of neural-glial 2 (NG2). NG2 is a member of the chondroitin sulfate proteoglycan family, a family of molecules known to exhibit inhibitory effects on neurons. Therefore, the finding that cells expressing this molecule can stabilize dystrophic endings of neurons after injury was surprising. Here we utilized a dorsal column crush injury to investigate the interactions that occur between this progenitor cell population and the injured neurons. We found that injured fibers persist in an area of high NG2 expression for weeks after injury. Using an NG2+ cell population cultured from adult spinal cords in co-cultures with adult dorsal root ganglion neurons, we observed that these neurons are not inhibited by the NG2+ cell surface, but actually prefer to grow upon the surface of these cells over other growth-permissive substrates. Over time, the cultured neurons no longer extend processes off the NG2+ cell surface, an adhesion that can be overcome at acute timepoints by degrading the NG2 glycosaminoglycan side chains with an enzyme known as chondroitinase ABC. However, by five days in co-culture, chondroitinase is no longer effective at releasing neurites from the NG2+ cell surface, suggesting these connections become more permanent. Studies using various concentrations of proteoglycans and growth-permissive extracellular matrix molecules laminin or fibronectin further illustrate the role of proteoglycans in mediating the entrapment phenomenon. By two days in vitro, neurons cultured on a monolayer of NG2+ cells begin to express synaptic vesicle proteins in puncta along their neurites. Electron microscopy and FM studies were used to further investigate the interaction of these two cell types in culture and suggest that these two cells form synaptic-like connections in a dish. Similiarly, at 21 days after injury, labeled dystrophic fibers begin to express synaptic markers when associated with NG2+ cells in vivo. Double-conditioning of the sciatic nerve after the dorsal column crush allowed fibers to regenerate beyond the rostral end of the glial scar, as has been shown previously. The fibers that reach beyond the rostral end of the lesion appear to express less synaptic protein than those that remain associated with the NG2+ cell population at the caudal end of the lesion. Consistent with the idea that NG2 plays a role in stabilizing dystrophic fibers, we observed that injured axons in NG2 KO mice dieback further than those of wild-type mice at 14 days after injury. These data suggest a novel cause of regeneration failure, entrapment, which adds to the complexity of achieving successful regeneration after SCI.In a separate study within this… Advisors/Committee Members: Landmesser, Lynn (Committee Chair), Silver, Jerry (Advisor).

Subjects/Keywords: Neurosciences; NG2; chondroitin sulfate proteoglycans; spinal cord injury, axonal dieback; regeneration; glial scar; spinal cord; entrapment; neuroscience; oligodendrocyte precursor cells

…the rostral end of the glial scar, as has been shown previously. The fibers that reach… …to cross the inhibitory rim of an in vitro model of the glial scar through an MMP-2… …is often referred to as the glial scar, because it has long been thought to be made up… …recruited to the site of injury. The glial scar provides both a physical and chemical barrier to… …have also been shown to inhibit neurite outgrowth. Glial scar formation Injury leads to the…

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APA (6^th Edition):

Filous, Angela R, P. D. (2014). The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1396605992

Chicago Manual of Style (16^th Edition):

Filous, Angela R, Ph D. “The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury.” 2014. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed February 25, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1396605992.

MLA Handbook (7^th Edition):

Filous, Angela R, Ph D. “The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury.” 2014. Web. 25 Feb 2021.

Vancouver:

Filous, Angela R PD. The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2014. [cited 2021 Feb 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1396605992.

Council of Science Editors:

Filous, Angela R PD. The Role of NG2+ Cells in Regeneration Failure After Spinal Cord Injury. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2014. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1396605992

25. Lang, Bradley Thomas. THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY.

Degree: PhD, Neurosciences, 2015, Case Western Reserve University School of Graduate Studies

URL: http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755

► Contusive spinal cord injury (SCI) is a devastating condition that leads to permanent disability due to the lack of neuronal regeneration and functional plasticity. It… (more)

Subjects/Keywords: Biomedical Research; Biology; Neurobiology; Neurology; Neurosciences; Spinal Cord Injury; Regenerative Medicine; Chondroitin Sulfate Proteoglycans; PTPsigma; Protein Tyrosine Phosphatase Sigma; Receptor Protein Tyrosine Phosphatase Sigma; Axonal Regeneration; Axonal Plasticity; Glial Scar

…glial scar Figure 44 171 Correlation between lesion size and behavioral recovery Figure 45… …upregulation of glial derived chondroitin sulfate proteoglycans (CSPGs) within the scar… …A.P. Tran, and J. Silver (2014). Functional regeneration beyond the glial scar… …characterization of the glial scar The primary barrier to regenerating axons in the CNS is the glial scar… …glial scar are reactive astrocytes, which become hypertrophic as they increase expression of…

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APA (6^th Edition):

Lang, B. T. (2015). THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY. (Doctoral Dissertation). Case Western Reserve University School of Graduate Studies. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755

Chicago Manual of Style (16^th Edition):

Lang, Bradley Thomas. “THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY.” 2015. Doctoral Dissertation, Case Western Reserve University School of Graduate Studies. Accessed February 25, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755.

MLA Handbook (7^th Edition):

Lang, Bradley Thomas. “THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY.” 2015. Web. 25 Feb 2021.

Vancouver:

Lang BT. THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY. [Internet] [Doctoral dissertation]. Case Western Reserve University School of Graduate Studies; 2015. [cited 2021 Feb 25]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755.

Council of Science Editors:

Lang BT. THE ROLE OF PTPs IN REGENERATION FAILURE FOLLOWING SPINAL CORD INJURY. [Doctoral Dissertation]. Case Western Reserve University School of Graduate Studies; 2015. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=case1417619755

26. Nicola, Fabrício do Couto. Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular.

Degree: 2017, Universidade do Rio Grande do Sul

URL: http://hdl.handle.net/10183/170284

►

A lesão medular (LM) é uma patologia incapacitante que resulta em déficits sensoriais e motores. No Brasil, a incidência anual é de 30 novos casos… (more)

▼

A lesão medular (LM) é uma patologia incapacitante que resulta em déficits sensoriais e motores. No Brasil, a incidência anual é de 30 novos casos de lesão medular a cada 1 milhão de indivíduos e, infelizmente, a LM permanece sem um tratamento eficaz. Células-tronco derivadas do dente decíduo humano estão entre as potenciais fontes de células-tronco para transplante após a lesão medular, cujo objetivo é de promover a proteção ou a recuperação da lesão na medula espinal. Buscou-se nesta tese avaliar os efeitos do transplante, uma hora após a lesão, das células tronco de dente decíduo humano (SHED) no período agudo, subagudo e crônico sobre a neuroproteção, proteção tecidual e recuperação funcional em ratos Wistar submetidos à lesão medular por contusão. Os principais objetivos foram: a) investigar os efeitos do transplante das SHED sobre a recuperação funcional, volume da lesão e morte neuronal; b) verificar os efeitos do transplante sobre as células progenitoras, formação da cicatriz glial e modificações astrocitárias após o modelo de contusão medular Observou-se a melhora na recuperação funcional, redução do volume da lesão e morte neuronal na medula espinal dos animais que receberam o transplante de SHED após a lesão medular. As SHED aumentam o número de células precursoras na medula espinal, no período subagudo, reduzem a expressão da proteína fibrilar glial ácida (GFAP) e aumentam a expressão do canal retificador de influxo de potássio 4.1, ambas proteínas astrocitárias. Concluímos que o transplante de células-tronco derivadas do dente decíduo humano após a lesão medular promove a recuperação funcional a partir do efeito neuroprotetor iniciado na fase aguda, confirmado pelo maior número de neurônios motores presentes seis semanas após a contusão. As SHED são capazes de aumentar o número de células precursoras e de produzir modificações astrocitárias na medula espinal de ratos lesados na fase subaguda, reduzindo a formação da cicatriz glial.

Spinal cord injury (SCI) is a disabling condition that results in sensory and motor deficits. The estimated annual incidence in Brazil is of 30 new cases of spinal cord injury per 1 million of individuals; unfortunately SCI remains without an effective treatment. Stem cells from human exfoliated deciduous teeth (SHED) are one among potential sources of stem cells for transplantation after spinal cord injury in order to promote protection or tissue and functional recovery after spinal cord injury. The aim of this Thesis was to evaluate the effects of stem cells from human exfoliated deciduous teeth (SHED) transplantation, one hour after lesion, in the acute, subacute and chronic phases on neuroprotection, tissue protection and functional recovery in Wistar rats submitted to spinal cord injury by contusion The main goals were: a) to investigate the effects of SHED transplantation on functional recovery, lesion volume, and neuronal death; b) to verify the effects of the transplantation on the progenitor cells number, glial scar formation and astrocytic modifications after…

Advisors/Committee Members: Netto, Carlos Alexandre.

Subjects/Keywords: Traumatismos da medula espinal; Spinal cord injury; Transplante de células-tronco; Mesenchymal stem cell; Células-tronco mesenquimais; Dental pulp stem cell; Dente decíduo; Tissue protection; Neuroprotection; Neuroproteção; Regeneração da medula espinal; Cell death; Apoptosis; Neurônios; Astrogliosis; Apoptose; Proteína glial fibrilar ácida; Glial scar; Proteínas S100; Progenitor cells; Functional recovery

…transplantation on the progenitor cells number, glial scar formation and astrocytic modifications after… …subacute phase, reducing glial scar formation. Key-words: Spinal cord injury, mesenchymal stem… …astrogliosis, glial scar, progenitor cells, functional recovery. XI 1. INTRODUÇÃO A lesão medular… …cicatriz glial e modificações astrocitárias após o modelo de contusão medular. Observou-se a… …proteína fibrilar glial ácida (GFAP) e aumentam a expressão do canal retificador de…

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APA (6^th Edition):

Nicola, F. d. C. (2017). Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/170284

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nicola, Fabrício do Couto. “Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular.” 2017. Thesis, Universidade do Rio Grande do Sul. Accessed February 25, 2021. http://hdl.handle.net/10183/170284.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nicola, Fabrício do Couto. “Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular.” 2017. Web. 25 Feb 2021.

Vancouver:

Nicola FdC. Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2017. [cited 2021 Feb 25]. Available from: http://hdl.handle.net/10183/170284.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nicola FdC. Efeito neuroprotetor do transplante de células-tronco mesenquimais derivadas de dente decíduo humano em ratos Wistar submetidos à lesão medular. [Thesis]. Universidade do Rio Grande do Sul; 2017. Available from: http://hdl.handle.net/10183/170284

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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