Details
- Autor(en) / Beteiligte
- Titel
- Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice
- Ist Teil von
- PloS one, 2012-07, Vol.7 (7), p.e41229
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0041229Titel-ID: cdi_plos_journals_1326219450
- Format
- –
- Schlagworte
- Animals, Apoptosis, Aquaporin 4, Aquaporin 4 - biosynthesis, Aquaporins, Astrocytes - metabolism, Biology, Brain, Brain - metabolism, Brain damage, Brain Edema - metabolism, Brain injuries, Brain Injuries - physiopathology, Cerebral edema, Cerebrum, Cortex, Drinking water, Drug delivery systems, Edema, Free radicals, Glial fibrillary acidic protein, Growth factors, Head injuries, Health sciences, Homeopathy, IL-1β, Immunohistochemistry - methods, Inflammation, Injuries, Injury prevention, Interleukin, Interleukin-1beta - metabolism, Interleukins, Intermediate filament proteins, Intracranial Pressure, Intravenous administration, Magnetic Resonance Imaging - methods, Male, Materia medica and therapeutics, Medicine, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Confocal - methods, Models, Neurological, Mortality, Neuroglia - metabolism, Neurosurgery, Parenchyma, Prevention, Proteins, Receptors, Purinergic P2X7 - genetics, Receptors, Purinergic P2X7 - metabolism, Rodents, Therapeutics, Traumatic brain injury