Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

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. Unfortunate...

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Autores principales:	Donald E Kimbler, Jessica Shields, Nathan Yanasak, John R Vender, Krishnan M Dhandapani
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/236b3b8fcad548769268d377e79696a7
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spelling	oai:doaj.org-article:236b3b8fcad548769268d377e79696a72021-11-18T07:12:10ZActivation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.1932-620310.1371/journal.pone.0041229https://doaj.org/article/236b3b8fcad548769268d377e79696a72012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22815977/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Traumatic 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-1β (IL-1β) 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-1β 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.Donald E KimblerJessica ShieldsNathan YanasakJohn R VenderKrishnan M DhandapaniPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41229 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Donald E Kimbler Jessica Shields Nathan Yanasak John R Vender Krishnan M Dhandapani Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
description	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-1β (IL-1β) 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-1β 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.
format	article
author	Donald E Kimbler Jessica Shields Nathan Yanasak John R Vender Krishnan M Dhandapani
author_facet	Donald E Kimbler Jessica Shields Nathan Yanasak John R Vender Krishnan M Dhandapani
author_sort	Donald E Kimbler
title	Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
title_short	Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
title_full	Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
title_fullStr	Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
title_full_unstemmed	Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
title_sort	activation of p2x7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/236b3b8fcad548769268d377e79696a7
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Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

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