Accession Number PB2013-103246
Title Therapeutic Targeting of P2X7 after TBI.
Publication Date Jul 2012
Media Count 41p
Personal Author K. Donald
Abstract Traumatic 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-1ss (IL-1ss) and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG), a clinically non-toxic P2X7 inhibitor, inhibited IL-1ss expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed 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 attenuated 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.
Keywords Brain injury
Cause of death
Disability
INtracranial Pressure(ICP)
Life-threatening
Medical therapies
Neurobehavioral outcomes
Traumatic Brain Injury(TBI)


 
Source Agency TriService Nursing Research Program/Uniform Services Univ. of the Health Sciences
NTIS Subject Category 57U - Public Health & Industrial Medicine
57E - Clinical Medicine
68G - Environmental Health & Safety
Corporate Author Medical Coll. of Georgia, Augusta.
Document Type Technical report
Title Note N/A
NTIS Issue Number 1307
Contract Number N/A

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