Spreading Depolarizations of Cerebral Cortex after Brain Injury: Mechanism of Injury Progression and Relevance to Military Neurotrauma

Based on media reports, neurotrauma has emerged as the signature wound in the Global War on Terrorism (GWOT). Brain trauma is frequently the result of blast injury, producing a unique syndrome with a high incidence of traumatic sub-arachnoid hemorrhage (SAH) and vasospasm. Cortical spreading depolarizations (CSD) are a pathologic short-circuiting of brain function that cause secondary brain damage in animal models of cerebral ischemia. We investigated the role of CSD as a novel pathogenic mechanism in civilians with SAH and traumatic brain injury (TBI). In both diseases, CSD occurs with a high incidence (>50%) and is associated with progressive cerebral metabolic compromise, tissue infarction, and poor neurologic recovery. Results suggest CSD may be mitigated by therapeutic hypothermia. We speculate that CSD underlies delayed deterioration in GWOT casualties who have characteristics of both civilian TBI and SAH. Based on civilian incidence, it is estimated that at least 2,716 U.S. service members in Operation Iraqi Freedom (OIF) have experienced CSD. We consider it a vital obligation to discover the pathophysiologic and therapeutic implications of CSD in order to improve survivability and recovery from military neurotrauma.