Therapeutic Targeting of P2X7 after TBI

Traumatic brain injury (TBI) is the leading cause of death and disability worldwide and is a growing basis of morbidity in deployed Soldiers.  Although preventative measures may reduce the incidence of TBI, 22-29% of all wounded Soldiers from OIF/OEF suffer a TBI, including 43% of Soldiers experiencing a blast injury making TBI the “signature wound” of current operations(4). Brain edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP), brain herniation, and a poor prognosis following head injury. Clinically, the degree of swelling on the first computed tomography (CT) scan directly correlates with patient   outcome, demonstrating the need   to limit brain edema following head injury. Unfortunately, current medical therapies do not effectively control brain edema and neurosurgical approaches to alleviate increased ICP are invasive and of limited utility.   Furthermore, a limited number of neurosurgical staff are deployed in theater, logistically complicating acute intervention in these wounded Soldiers.

The goal of this study is to elucidate molecular and cellular mechanisms that promote cerebral edema, which may aid in the development of novel therapeutics to limit neurological dysfunction and reduce the incidence of PTSD in wounded Soldiers returning from deployments. Herein, we propose a mechanistic hypothesis to explain the etiology of cerebral edema, which if proven, could improve outcomes after TBI.

Final Report is available on NTRL: https://ntrl.ntis.gov/NTRL/dashboard/searchResults/titleDetail/PB2013103...