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dc.contributor.authorKimbler Jr, Donald E
dc.date.accessioned2021-02-22T20:15:55Z
dc.date.available2021-02-22T20:15:55Z
dc.date.issued2012-02
dc.identifier.urien
dc.identifier.urihttp://hdl.handle.net/10675.2/623871
dc.descriptionThe file you are attempting to access is currently restricted to Augusta University. Please log in with your NetID if off campus.
dc.description.abstractTraumatic brain injury (TBI) is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP) and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part, to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice) of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-I~ (IL-1~) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, the clinically useful P2X7 inhibitor, brilliant blue G (BBG), inhibited the expression of IL-1~, limited edemic development and prevented the development of post-traumatic depression and anxiety. The beneficial effects of BBG were observed following either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP), a reactive astrocyte marker, and reduced the expression of aquaporin-4 (AQP4), an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.en_US
dc.language.isoen_USen_US
dc.publisherGeorgia Health Sciences Universityen_US
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.en_US
dc.subjectNeurotraumaen_US
dc.subjectIntracranial pressureen_US
dc.subjectInnate immunityen_US
dc.subjectNeuroinflammationen_US
dc.subjectATPen_US
dc.subjectPurinergicen_US
dc.subjectBrilliant Blue Gen_US
dc.subjectControlled Cortical Impacten_US
dc.titleTherapeutic Targeting of P2X7 after Traumatic Brain Injuryen_US
dc.typeDissertationen_US
dc.contributor.departmentDepartment of Neuroscience and Regenerative Medicineen_US
dc.description.advisorDhandapani, Krishnan
dc.description.majorMajor in Neuroscienceen_US
dc.description.committeeBrann, Darrell
dc.description.committeeMcClusky, Lynnette
dc.description.committeeVender, John
dc.description.committeeSchumacher, Autumn
dc.description.degreeDoctor of Philosophyen_US
dc.embargoen
refterms.dateFOA2021-02-22T20:15:56Z


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