subject:(Chondroitinase ABC)

National University of Ireland – Galway

1. 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 (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 March 08, 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. 08 Mar 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 Mar 08]. 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

2. Anandakumaran, Priya Nivashini. Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord.

Degree: 2016, University of Toronto

URL: http://hdl.handle.net/1807/97273

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The inability of injured axons to regenerate across the lesion that forms following a spinal cord injury is largely attributed to their reduced growth capacity,… (more)

Subjects/Keywords: Biomaterials; Cell Transplantation; Chondroitinase ABC; Hydrogels; Neuronal Precursor Cells; Spinal Cord Injury; 0541

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APA (6^th Edition):

Anandakumaran, P. N. (2016). Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/97273

Chicago Manual of Style (16^th Edition):

Anandakumaran, Priya Nivashini. “Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord.” 2016. Masters Thesis, University of Toronto. Accessed March 08, 2021. http://hdl.handle.net/1807/97273.

MLA Handbook (7^th Edition):

Anandakumaran, Priya Nivashini. “Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord.” 2016. Web. 08 Mar 2021.

Vancouver:

Anandakumaran PN. Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord. [Internet] [Masters thesis]. University of Toronto; 2016. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1807/97273.

Council of Science Editors:

Anandakumaran PN. Co-delivery of Chondroitinase ABC and Pre-differentiated Progeny of Human Neuroepithelial Cells in Hydrogels to the Injured Spinal Cord. [Masters Thesis]. University of Toronto; 2016. Available from: http://hdl.handle.net/1807/97273

3. Anderson, Michael David 1995-. THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.

Degree: 2019, University of Saskatchewan

URL: http://hdl.handle.net/10388/12299

► Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround subsets of neurons in the central nervous system (CNS). They help in maintaining a stable… (more)

▼ Perineuronal nets (PNNs) are specialized extracellular matrix structures that surround subsets of neurons in the central nervous system (CNS). They help in maintaining a stable excitatory-inhibitory balance in the brain, and the adult loss of PNNs can lead to a period of increased synaptic plasticity. Furthermore, the loss of PNNs can affect cortical networks and influence learning, memory, and cognition. The aim of this thesis was to test the effect that degrading PNNs in the medial prefrontal (mPFC) and posterior parietal (PPC) cortices had on spatial working memory (WM). To do this, the spatial WM of Long-Evans rats was measured using the trial unique, delayed nonmatching-to-location (TUNL) task in touchscreen-equipped operant conditioning chambers. Rats were trained in this task and then assigned to either a penicillinase (PEN) control or chondroitinase ABC (ChABC) treatment. ChABC is an enzyme that compromises the structure of PNNs by degrading one of their major components: chondroitin sulfate proteoglycans (CSPGs). Surgeries were performed to infuse these enzymes into the medial prefrontal cortex (mPFC) in a first set of rats and into the posterior parietal cortex (PPC) in a second set of rats. All rats were trained under a standard 6 s delay and then tested under 4 conditions: a 6 s delay, a variable 2 s or 6 s delay, a 2 s delay with a 1s inter-trial interval (interference condition), and a 20 s delay. Rats that received mPFC ChABC infusions initially performed better than controls in the 20 s delay condition, but did not perform any differently in any of the other three conditions. Rats that received PPC ChABC infusions did not perform significantly differently from controls in any condition. Immunohistochemical analysis confirmed that CSPGs were degraded in both cortical regions. This suggests that PNNs in the mPFC are involved in learning a novel delay in a spatial WM task, but that they are not essential for general spatial WM function. Furthermore, it appears that PNNs in the PPC are not involved in spatial WM. Ultimately, these findings contribute to a growing body of literature that explores how cortical PNNs are involved in cognition. Advisors/Committee Members: Howland, John G, Baillie, Landon, Ianowski, Juan, Borowsky, Ron.

Subjects/Keywords: perineuronal nets; Chondroitinase ABC; medial prefrontal cortex; posterior parietal cortex

…Neuropsychological Test Automated Battery ChABC Chondroitinase ABC CNS Central Nervous System CSPGs… …developed. Chondroitinase ABC (ChABC) and hyaluronidase are two enzyme treatments that… …enzyme chondroitinase ABC (ChABC), which cleaves apart CSPGs. We then measured the… …enzyme chondroitinase ABC (ChABC) (Lee et al. 2009). Interestingly, the… …trained on TUNL to criterion. Chondroitinase ABC or penicillinase was then locally infused into…

1 more image…

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APA (6^th Edition):

Anderson, M. D. 1. (2019). THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/12299

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):

Anderson, Michael David 1995-. “THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.” 2019. Thesis, University of Saskatchewan. Accessed March 08, 2021. http://hdl.handle.net/10388/12299.

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

MLA Handbook (7^th Edition):

Anderson, Michael David 1995-. “THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS.” 2019. Web. 08 Mar 2021.

Vancouver:

Anderson MD1. THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. [Internet] [Thesis]. University of Saskatchewan; 2019. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10388/12299.

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

Council of Science Editors:

Anderson MD1. THE EFFECTS OF DEGRADING PERINEURONAL NETS IN THE MEDIAL PREFRONTAL AND POSTERIOR PARIETAL CORTICES ON THE SPATIAL WORKING MEMORY OF RATS. [Thesis]. University of Saskatchewan; 2019. Available from: http://hdl.handle.net/10388/12299

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

4. Bocabello, Renato Zonzini. O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos.

Degree: Mestrado, Anatomia dos Animais Domésticos e Silvestres, 2013, University of São Paulo

URL: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21112013-144847/ ;

►

Cerca de 0,005% da população mundial sofre de lesão medular. O processo regenerativo do tecido nervoso apresenta limitada capacidade para repor as células danificadas (JOHANSSON… (more)

▼

Cerca de 0,005% da população mundial sofre de lesão medular. O processo regenerativo do tecido nervoso apresenta limitada capacidade para repor as células danificadas (JOHANSSON et al., 1999) e produzir inibidores de crescimento dos axônios associados com a mielina para formação de cicatriz glial (OLSON, 2002). Apesar de resultados promissores, ainda existem controversas quanto ao uso de células-tronco. A eliminação da cicatriz glial, os benefícios de sua formação em diferentes fases e a avaliação da liberação de inibidores de crescimento axonal podem ser parâmetros de análise para o tratamento medular. A enzima condroitinase ABC atua nessa lesão. Neste trabalho avaliamos a interrupção do processo de liberação de inibidores axonais da cicatriz da glia em um tempo não agudo de 7 dias da lesão, sem descartar seus benefícios na fase de formação. Nosso objetivo foi utilizar terapia celular e estabelecer um protocolo de tratamento eficaz, criando uma linha de pesquisa nos estudos da lesão medular. Foi utilizado um grupo de coelhos experimental com realização de hemissecção dorsal e instituído o uso da condroitinase ABC, por aplicação, com micro injeção a curto prazo da lesão. Foi aplicada célula-tronco mesenquimal no foco da lesão após o tratamento da cicatriz da glia com a enzima. Avaliamos por imunohistoquimica a liberação de glial fibrillary acidic protein (GFAP) e sulfato de condroitina proteoglicano (SCPg) nos tecidos após o tratamento no qual foi pretendido fechar algumas lacunas e evitar falhas já descritas, e abrir uma nova esperança no tratamento de pacientes com lesão medular. Nossos resultados ainda mostraram um entendimento superficial sobre a enzima e sua ação sobre cicatrização da glia em associação com o implante celular. Foi aberta uma nova linha de questionamento sobre os benefícios causados à regeneração medular previamente a aplicação de células-tronco.

Around 0,005% of global human population is affected by Spinal Cord Injury (SCI). The regenerative process of neural tissue shows a limited capacity to replace damaged cells (JOHANSSON et al., 1999) and to produce growth inhibitors of associated axons with myelin to create glial scar (OLSON, 2002). Plenty of studies are being developed with stem cell and, despite successful results, there still are controversial opinions. The elimination of the glial scar, the benefits of its growth at different stages and the assessment of axonal growth inhibitorsŕelease can be parameters of analysis for treating spinal cord. The enzyme chondroitinase ABC acts in this lesion. In this paper we evaluated the release interruption of axonal inhibitors of glial scar in a non-acute 7 days term from injury, not disregarding its benefits during growth. Our goal was to use cell therapy and establish an effective treatment protocol, creating a research line for studies of spinal cord injury and its treatment. A group of rabbits was used under experimental model, conducting dorsal hemisection and application of chondroitinase ABC with micro injection in short-term injury.…

Advisors/Committee Members: Ambrosio, Carlos Eduardo.

Subjects/Keywords: Células-tronco; Chondroitinase ABC; Condroitinase ABC; Lesão medular; Spinal cord injury; Stem cells

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

APA (6^th Edition):

Bocabello, R. Z. (2013). O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos. (Masters Thesis). University of São Paulo. Retrieved from http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21112013-144847/ ;

Chicago Manual of Style (16^th Edition):

Bocabello, Renato Zonzini. “O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos.” 2013. Masters Thesis, University of São Paulo. Accessed March 08, 2021. http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21112013-144847/ ;.

MLA Handbook (7^th Edition):

Bocabello, Renato Zonzini. “O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos.” 2013. Web. 08 Mar 2021.

Vancouver:

Bocabello RZ. O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos. [Internet] [Masters thesis]. University of São Paulo; 2013. [cited 2021 Mar 08]. Available from: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21112013-144847/ ;.

Council of Science Editors:

Bocabello RZ. O uso de condroitinase ABC combinada com células-tronco do epitélio olfatório de coelhos em modelo de lesão medular por hemissecção dorsal em coelhos. [Masters Thesis]. University of São Paulo; 2013. Available from: http://www.teses.usp.br/teses/disponiveis/10/10132/tde-21112013-144847/ ;

Vanderbilt University

5. Bowes, Charnese Peter-Gay. Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey.

Degree: PhD, Psychology, 2011, Vanderbilt University

URL: http://hdl.handle.net/1803/12434

► The importance of accurate cortical representation and processing of hand use is clearly appreciated when one considers the behavioral deficits observed after the dorsal columns… (more)

▼ The importance of accurate cortical representation and processing of hand use is clearly appreciated when one considers the behavioral deficits observed after the dorsal columns have been interrupted. Animals experience gross deficits in their ability to accurately guide the affected hand, and additionally, once the item is within its grasp, the animal may keep looking for it due to the loss of tactile sensation. We were able to conclude that somatosensory cortical areas including 3b, 3a, area 1 and possibly area 2 undergo considerable reorganization subsequent to dorsal column injury in the marmoset. We posited that one likely source of this reorganization is the sprouting of collateral axons of primary afferent fibers that remain intact after injury. Whether these postsynaptic nuclei are appropriate targets that go on to make connections with corresponding parts of the body representation in cortex plays a crucial role in determining if amplification of an appropriate signal will occur, or if misperception of the source of input takes place. Prior studies in rats indicate that application of chondroitinase ABC (chABC) to the dorsal column nuclei subsequent to dorsal column pathway damage leads to functional reactive sprouting. We sought to determine how somatosensory cortical organization is affected subsequent to dorsal column pathway damage and chABC application to the cuneate nucleus in squirrel monkeys. In the chABC-treated animals, these recordings showed that cortical territories once activated by deafferented peripheral inputs had become primarily responsive to the D1 afferents that remained intact after the lesion. It will be necessary to not only promote the eventual formation of new and functional synapses but also to provide the guidance necessary for these new circuits to confer behavioral benefits to those affected by SCI. Advisors/Committee Members: Troy Hackett (committee member), Sohee Park (committee member), Ford Ebner (committee member), Jon Kaas (Committee Chair).

Subjects/Keywords: dorsal column; chondroitinase ABC; spinal cord injury; monkey

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

APA (6^th Edition):

Bowes, C. P. (2011). Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/12434

Chicago Manual of Style (16^th Edition):

Bowes, Charnese Peter-Gay. “Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey.” 2011. Doctoral Dissertation, Vanderbilt University. Accessed March 08, 2021. http://hdl.handle.net/1803/12434.

MLA Handbook (7^th Edition):

Bowes, Charnese Peter-Gay. “Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey.” 2011. Web. 08 Mar 2021.

Vancouver:

Bowes CP. Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey. [Internet] [Doctoral dissertation]. Vanderbilt University; 2011. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1803/12434.

Council of Science Editors:

Bowes CP. Reorganization of somatosensory cortex subsequent to dorsal column injury: a study of the marmoset and the squirrel monkey. [Doctoral Dissertation]. Vanderbilt University; 2011. Available from: http://hdl.handle.net/1803/12434

Georgia Tech

6. Lee, Hyun-Jung. Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury.

Degree: PhD, Biomedical Engineering, 2009, Georgia Tech

URL: http://hdl.handle.net/1853/31734

► Chondroitin sulfate proteoglycans (CSPGs) are one major class of axon growth inhibitors that are upregulated and accumulated around the lesion site after spinal cord injury… (more)

▼ Chondroitin sulfate proteoglycans (CSPGs) are one major class of axon growth inhibitors that are upregulated and accumulated around the lesion site after spinal cord injury (SCI), and result in regenerative failure. To overcome CSPG-mediated inhibition, digestion of CSPGs with chondroitinase ABC (chABC) has been explored and it has shown promising results. chABC digests glycosaminoglycan chains on CSPGs and can thereby enhance axonal regeneration and promote functional recovery when delivered at the site of injury. However, chABC has a crucial limitation; it is thermally unstable and loses its enzymatic activity rapidly at 37 ºC. Therefore, it necessitates the use of repeated injections or local infusions with a pump for days to weeks to provide fresh chABC to retain its enzymatic activity. Maintaining these infusion systems is invasive and clinically problematic. In this dissertation, three studies are reported that demonstrate our strategy to overcome current limitations of using chABC and develop a delivery system for facilitating chABC treatment after SCI: First, we enhanced the thermostability of chABC by adding trehalose, a protein stabilizer, and developed a system for its sustained local delivery in vivo. Enzymatic activity was assayed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and dimethylmethylene blue (DMMB), and conformational change of the enzyme was measured via circular dichroism (CD) with and without trehalose. When stabilized with trehalose, chABC remained enzymatically active at 37 ºC for up to 4 weeks in vitro. We developed a lipid microtube-agarose hydrogel delivery system for a sustained release and showed that chABC released from the delivery system is still functionally active and slowly released over 2 weeks in vitro. Second, the hydrogel-microtube system was used to locally deliver chABC over two weeks at the lesion site following a dorsal over hemisection injury at T10. The scaffold consisting of hydrogel and chABC loaded lipid microtubes was implanted at the top of the lesion site immediately following injury. To determine effectiveness of topical delivery of thermostabilized chABC, animal groups treated with single injection or gel scaffold implantation of chABC and penicillinase (P'ase) were included as controls. Two weeks after surgery, the functionality of released chABC and the cellular responses were examined by immunohistological analysis with 3B3, CS-56, GFAP and Wisteria floribunda agglutinin (WFA). The results demonstrated that thermostabilized chABC was successfully delivered slowly and locally without the need for an indwelling catheter by using the hydrogel-microtube delivery system in vivo. The results demonstrated that released chABC from the gel scaffold effectively digested CSPGs, and therefore, there were significant differences in CSPG digestion at the lesion site between groups treated with chABC loaded microtube-hydrogel scaffolds and controls. Third, a long term in vivo study (45 days) was conducted to examine axonal… Advisors/Committee Members: Ravi V. Bellamkonda (Committee Chair), Andreas Bommarius (Committee Member), Andrés J. García (Committee Member), Niren Murthy (Committee Member), Robert J. McKeon (Committee Member).

Subjects/Keywords: Lipid microtube; Hydrogel; Regeneration; Chondroitin sulfate proteoglycan; Spinal cord injury; Chondroitinase ABC; Chondroitin sulfates; Protein engineering; Spinal cord Wounds and injuries; Spinal cord Regeneration

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

APA (6^th Edition):

Lee, H. (2009). Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury. (Doctoral Dissertation). Georgia Tech. Retrieved from http://hdl.handle.net/1853/31734

Chicago Manual of Style (16^th Edition):

Lee, Hyun-Jung. “Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury.” 2009. Doctoral Dissertation, Georgia Tech. Accessed March 08, 2021. http://hdl.handle.net/1853/31734.

MLA Handbook (7^th Edition):

Lee, Hyun-Jung. “Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury.” 2009. Web. 08 Mar 2021.

Vancouver:

Lee H. Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury. [Internet] [Doctoral dissertation]. Georgia Tech; 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1853/31734.

Council of Science Editors:

Lee H. Delivery of thermostabilized chondroitinase ABC enhances axonal sprouting and functional recovery after spinal cord injury. [Doctoral Dissertation]. Georgia Tech; 2009. Available from: http://hdl.handle.net/1853/31734

University of California – San Diego

7. Liang, Justine. Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment.

Degree: Biology, 2016, University of California – San Diego

URL: http://www.escholarship.org/uc/item/02t8c2w9

► Several factors contribute to the lack of repair following spinal cord injury, such as the lack of growth-promoting factors, poor intrinsic central nervous system regeneration… (more)

Subjects/Keywords: Neurosciences; Biology; axonal sprouting; chondroitinase ABC; chondroitin sulfate proteoglycan; corticospinal tract; rhesus monkey; spinal cord injury

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

APA (6^th Edition):

Liang, J. (2016). Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/02t8c2w9

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):

Liang, Justine. “Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment.” 2016. Thesis, University of California – San Diego. Accessed March 08, 2021. http://www.escholarship.org/uc/item/02t8c2w9.

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

MLA Handbook (7^th Edition):

Liang, Justine. “Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment.” 2016. Web. 08 Mar 2021.

Vancouver:

Liang J. Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Mar 08]. Available from: http://www.escholarship.org/uc/item/02t8c2w9.

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

Council of Science Editors:

Liang J. Chondroitinase ABC Administration in a Non-Human Primate Model of Spinal Cord Injury: Functional and Anatomical Assessment. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/02t8c2w9

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

Rice University

8. Natoli, Roman M. Impact loading and functional tissue engineering of articular cartilage.

Degree: PhD, Engineering, 2009, Rice University

URL: http://hdl.handle.net/1911/88472

► This thesis presents two advances for alleviating the problem of articular cartilage degeneration: mitigating degradative changes that follow mechanically induced injuries and growing functional neo-cartilage… (more)

▼ This thesis presents two advances for alleviating the problem of articular cartilage degeneration: mitigating degradative changes that follow mechanically induced injuries and growing functional neo-cartilage for diseased tissue replacement. Experiments demonstrate that cartilage subjected to a single, non-surface disrupting 1.1 J (Low) impact experiences sufficient degeneration over 4 weeks to become functionally equivalent to tissue subjected to a single, surface disrupting 2.8 J (High) impact. By 24 hrs post High impact, cell death and sulfated glycosaminoglycan (sGAG) release increased, changes in gene expression distinguished injured from adjacent tissue, and compressive stiffness decreased. In contrast, Low impacted tissue did not show decreased compressive stiffness until 4 weeks, revealing that Low impacted tissue experiences a delayed biological response. Post-injury treatment with the polymer P188, growth factor IGF-I, or matrix metalloproteinase inhibitor doxycycline partially ameliorated cell death and sGAG loss, two detrimental changes that occurred following either Low or High impact. With 1 week of treatment after Low impact, P188 reduced cell death 75% and IGF-I decreased sGAG release 49%. Following High impact, doxycycline treatment reduced 1 and 2 week sGAG release by 30% and 38%, respectively. As a novel method for engineering functional replacement tissue to use in cases of established disease, the GAG degrading enzyme chondroitinase ABC (C-ABC) improved the tensile integrity of articular cartilage constructs grown with a scaffold-less approach. C-ABC application increased ultimate tensile strength and tensile stiffness, reaching values of 1.4 and 3.4 MPa, respectively. Moreover, construct collagen concentration was ∼22% by wet weight. Though C-ABC temporarily depleted sGAG, by 6 weeks no significant differences in compressive stiffness remained. Furthermore, chondrocyte phenotype was maintained, as constructs contained collagen type II, but not collagen type I. Decorin decreased following C-ABC treatment, but recovered during subsequent culture. The known ability of decorin to control collagen fibrillogenesis suggests a putative mechanism for C-ABC's effects. Diseased articular cartilage heals poorly. For patients, the last resort is total joint replacement, though its associated morbidity and the limited lifespan of its results drive the need for alternate treatment strategies. Decreasing degradative changes post-injury and increasing functional properties of engineered cartilage are two significant improvements. Advisors/Committee Members: Athanasiou, Kyriacos (advisor), Grande-Allen, Jane (committee member), Gustin, Michael (committee member).

Subjects/Keywords: Biomedical engineering; Medicine; Physiology; Health and environmental sciences; Applied sciences; Biological sciences; Tissue engineering; Articular cartilage; Mechanobiology; Biomechanics; Mechanotransduction; Osteoarthritis; Chondroitinase ABC

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APA (6^th Edition):

Natoli, R. M. (2009). Impact loading and functional tissue engineering of articular cartilage. (Doctoral Dissertation). Rice University. Retrieved from http://hdl.handle.net/1911/88472

Chicago Manual of Style (16^th Edition):

Natoli, Roman M. “Impact loading and functional tissue engineering of articular cartilage.” 2009. Doctoral Dissertation, Rice University. Accessed March 08, 2021. http://hdl.handle.net/1911/88472.

MLA Handbook (7^th Edition):

Natoli, Roman M. “Impact loading and functional tissue engineering of articular cartilage.” 2009. Web. 08 Mar 2021.

Vancouver:

Natoli RM. Impact loading and functional tissue engineering of articular cartilage. [Internet] [Doctoral dissertation]. Rice University; 2009. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1911/88472.

Council of Science Editors:

Natoli RM. Impact loading and functional tissue engineering of articular cartilage. [Doctoral Dissertation]. Rice University; 2009. Available from: http://hdl.handle.net/1911/88472

University of Toronto

9. 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

►

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)

▼

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 March 08, 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. 08 Mar 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 Mar 08]. 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 Bristol

10. Prager, Jon B. M. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.

Degree: PhD, 2020, University of Bristol

URL: http://hdl.handle.net/1983/71a834d7-a06a-46ed-8a18-32aed9dcd29e

► Intra-spinal transplantation of olfactory ensheathing cells (OECs) and delivery of chondroitinase ABC (chABC) have separately shown promise as therapies for spinal cord injury (SCI). Efficacy… (more)

▼ Intra-spinal transplantation of olfactory ensheathing cells (OECs) and delivery of chondroitinase ABC (chABC) have separately shown promise as therapies for spinal cord injury (SCI). Efficacy has been demonstrated for both these approaches in trials using dogs with naturally occurring SCI, a model which may represent a means of bridging the gap in translation between laboratory interventions and clinical treatments. However, their individual effect was limited and combination therapy, including a means to increase OEC survival, may improve outcomes. It was recently demonstrated that OECs can be modified to express chABC (OEC-chABC), providing a combination therapy and novel delivery method of chABC. This thesis builds on that work by testing the functional benefit of this modified OEC transplant in two rodent models of SCI, as well as delivery of OECs within hydrogels to increase cell survival. We tested the effect of canine OEC-chABC compared to OECs alone on forepaw reaching in an acute incomplete SCI model (dorsal column crush injury), demonstrating greater recovery in OEC-chABC transplanted animals and proof of concept of this therapy. We further tested the effect of canine OEC- chABC on locomotion in a more severe chronic thoracic contusion model, showing no significant behavioural recovery compared to controls in this xenotransplant model with low OEC survival. We used a chronic cervical dorsal column crush injury in rats to test injection of canine OECs encapsulated in collagen hydrogel, demonstrating an average 7.5-fold increase in surviving OEC number at 2 weeks after transplant. Stiffness matching between implant and host tissue is necessary to reduce inflammatory reaction and prevent iatrogenic damage. Therefore, to facilitate hydrogel delivery on clinics, and to address a knowledge gap in the literature regarding the in vivo stiffness of SCI, we established an intraoperative ultrasound elastography approach to stiffness matching in dogs with natural SCI.

Subjects/Keywords: Spinal Cord Injury; Olfactory Ensheathing Cell Transplantation; Chondroitinase ABC; Hydrogel Biomaterial; Stiffness Matching

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❌

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

APA (6^th Edition):

Prager, J. B. M. (2020). A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. (Doctoral Dissertation). University of Bristol. Retrieved from http://hdl.handle.net/1983/71a834d7-a06a-46ed-8a18-32aed9dcd29e

Chicago Manual of Style (16^th Edition):

Prager, Jon B M. “A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.” 2020. Doctoral Dissertation, University of Bristol. Accessed March 08, 2021. http://hdl.handle.net/1983/71a834d7-a06a-46ed-8a18-32aed9dcd29e.

MLA Handbook (7^th Edition):

Prager, Jon B M. “A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.” 2020. Web. 08 Mar 2021.

Vancouver:

Prager JBM. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. [Internet] [Doctoral dissertation]. University of Bristol; 2020. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1983/71a834d7-a06a-46ed-8a18-32aed9dcd29e.

Council of Science Editors:

Prager JBM. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. [Doctoral Dissertation]. University of Bristol; 2020. Available from: http://hdl.handle.net/1983/71a834d7-a06a-46ed-8a18-32aed9dcd29e

University of Bristol

11. Prager, Jon B. M. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.

Degree: PhD, 2020, University of Bristol

URL: https://research-information.bris.ac.uk/en/studentTheses/71a834d7-a06a-46ed-8a18-32aed9dcd29e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.809865

► Intra-spinal transplantation of olfactory ensheathing cells (OECs) and delivery of chondroitinase ABC (chABC) have separately shown promise as therapies for spinal cord injury (SCI). Efficacy… (more)

▼ Intra-spinal transplantation of olfactory ensheathing cells (OECs) and delivery of chondroitinase ABC (chABC) have separately shown promise as therapies for spinal cord injury (SCI). Efficacy has been demonstrated for both these approaches in trials using dogs with naturally occurring SCI, a model which may represent a means of bridging the gap in translation between laboratory interventions and clinical treatments. However, their individual effect was limited and combination therapy, including a means to increase OEC survival, may improve outcomes. It was recently demonstrated that OECs can be modified to express chABC (OEC-chABC), providing a combination therapy and novel delivery method of chABC. This thesis builds on that work by testing the functional benefit of this modified OEC transplant in two rodent models of SCI, as well as delivery of OECs within hydrogels to increase cell survival. We tested the effect of canine OEC-chABC compared to OECs alone on forepaw reaching in an acute incomplete SCI model (dorsal column crush injury), demonstrating greater recovery in OEC-chABC transplanted animals and proof of concept of this therapy. We further tested the effect of canine OEC- chABC on locomotion in a more severe chronic thoracic contusion model, showing no significant behavioural recovery compared to controls in this xenotransplant model with low OEC survival. We used a chronic cervical dorsal column crush injury in rats to test injection of canine OECs encapsulated in collagen hydrogel, demonstrating an average 7.5-fold increase in surviving OEC number at 2 weeks after transplant. Stiffness matching between implant and host tissue is necessary to reduce inflammatory reaction and prevent iatrogenic damage. Therefore, to facilitate hydrogel delivery on clinics, and to address a knowledge gap in the literature regarding the in vivo stiffness of SCI, we established an intraoperative ultrasound elastography approach to stiffness matching in dogs with natural SCI.

Subjects/Keywords: Spinal Cord Injury; Olfactory Ensheathing Cell Transplantation; Chondroitinase ABC; Hydrogel Biomaterial; Stiffness Matching

Record Details Similar Records Cite « Share

❌

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

APA (6^th Edition):

Prager, J. B. M. (2020). A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. (Doctoral Dissertation). University of Bristol. Retrieved from https://research-information.bris.ac.uk/en/studentTheses/71a834d7-a06a-46ed-8a18-32aed9dcd29e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.809865

Chicago Manual of Style (16^th Edition):

Prager, Jon B M. “A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.” 2020. Doctoral Dissertation, University of Bristol. Accessed March 08, 2021. https://research-information.bris.ac.uk/en/studentTheses/71a834d7-a06a-46ed-8a18-32aed9dcd29e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.809865.

MLA Handbook (7^th Edition):

Prager, Jon B M. “A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury.” 2020. Web. 08 Mar 2021.

Vancouver:

Prager JBM. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. [Internet] [Doctoral dissertation]. University of Bristol; 2020. [cited 2021 Mar 08]. Available from: https://research-information.bris.ac.uk/en/studentTheses/71a834d7-a06a-46ed-8a18-32aed9dcd29e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.809865.

Council of Science Editors:

Prager JBM. A genetic and tissue-engineering approach to improving canine olfactory ensheathing cell transplant for spinal cord injury. [Doctoral Dissertation]. University of Bristol; 2020. Available from: https://research-information.bris.ac.uk/en/studentTheses/71a834d7-a06a-46ed-8a18-32aed9dcd29e ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.809865

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