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You searched for +publisher:"University of Manitoba" +contributor:("Eftekharpour, Eftekhar (Physiology and Pathophysiology) Werbowetski-Ogilvie, Tamra (Biochemistry and Medical Genetics) Hannila, Sari (Human Anatomy and Cell Science) Fouad, Karim (University of Alberta)"). One record found.

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University of Manitoba

1. 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

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 (6th 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 (16th 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 October 20, 2019. 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 (7th Edition):

Dyck, Scott. “Elucidating the role and mechanisms of CSPGs in modulating endogenous repair processes in spinal cord injury.” 2015. Web. 20 Oct 2019.

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 2019 Oct 20]. 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

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