The Role of Toll-Like Receptor 4 in the Secondary Pathogenesis of Spinal Cord Injury

Hdl Handle:
http://hdl.handle.net/10675.2/325496
Title:
The Role of Toll-Like Receptor 4 in the Secondary Pathogenesis of Spinal Cord Injury
Authors:
Fessler, David R.
Abstract:
Spinal cord injury (SCI) is a leading cause of paralysis and disability worldwide, however no successful treatments have been developed partly due to a lack of understanding of SCI pathophysiology. This study established a model of compression SCI for investigation of the proinflammatory receptor, toll-like receptor 4. The model was validated measuring motor function, lesion size, Fluoro-Jade B staining, and western blots of PARP cleavage and 3-nitrotyrosine. Western blots and immunohistochemistry showed a biphasic upregulation of TLR4 in neurons after injury with peaks at 6 and 48 hours post-SCI. TLR4 mutant mice showed diminished lesion size, Fluoro-Jade B and hydroethidine staining, as well as improved motor function; and pre-treatment with TLR4 antagonist, VGX-1027, in wild type (WT) mice improved motor function as well. GP91 expression was unchanged in TLR4 mutants, suggesting changes in superoxide production may be NOX2 independent. This study suggests that targeting TLR4 may be viable therapeutic strategy for the repair/treatment of SCI.
Issue Date:
31-Jul-2016
URI:
http://hdl.handle.net/10675.2/325496
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/1552473055?accountid=12365
Type:
Dissertation
Language:
en
Appears in Collections:
Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorFessler, David R.en
dc.date.accessioned2014-08-28T00:46:12Z-
dc.date.available2014-08-28T00:46:12Z-
dc.date.issued2016-07-31-
dc.identifier.urihttp://hdl.handle.net/10675.2/325496-
dc.description.abstractSpinal cord injury (SCI) is a leading cause of paralysis and disability worldwide, however no successful treatments have been developed partly due to a lack of understanding of SCI pathophysiology. This study established a model of compression SCI for investigation of the proinflammatory receptor, toll-like receptor 4. The model was validated measuring motor function, lesion size, Fluoro-Jade B staining, and western blots of PARP cleavage and 3-nitrotyrosine. Western blots and immunohistochemistry showed a biphasic upregulation of TLR4 in neurons after injury with peaks at 6 and 48 hours post-SCI. TLR4 mutant mice showed diminished lesion size, Fluoro-Jade B and hydroethidine staining, as well as improved motor function; and pre-treatment with TLR4 antagonist, VGX-1027, in wild type (WT) mice improved motor function as well. GP91 expression was unchanged in TLR4 mutants, suggesting changes in superoxide production may be NOX2 independent. This study suggests that targeting TLR4 may be viable therapeutic strategy for the repair/treatment of SCI.en
dc.language.isoenen
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/1552473055?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
dc.subjectspinal cord injuryen
dc.subjectSCIen
dc.subjectneurotraumaen
dc.subjectInnate Immunityen
dc.subjectOxidative stressen
dc.subjectsuperoxideen
dc.subjectTLR4en
dc.subjectVGX-1027en
dc.titleThe Role of Toll-Like Receptor 4 in the Secondary Pathogenesis of Spinal Cord Injuryen
dc.typeDissertationen
dc.description.advisorDhandapani, Krishnan M.en
dc.description.committeeBrann, Darrell; Vender, John; Hamrick, Mark; Pillai, Anilen
dc.description.degreeDoctor of Philosophy (Ph.D.)en
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