Neuroprotective Mechanisms of Oxygen and Ethanol: A Potential Combination Therapy in Stroke

Currently, stroke researchers are racing to develop neuroprotective strategies that shield the brain from ischemia-induced injury. To date, neuroprotective agents that have shown promise in animal studies have failed in clinical trials. Since the pathophysiology of ischemic stroke exploits numerous pathways leading to cellular injury, a combination of neuroprotective agents may offer substantially better results than a single agent alone - by intervening in multiple mechanisms. In this paper, we consider an approach using combination therapy with normobaric oxygen (NBO) and ethanol. Studies indicate that NBO therapy improves tissue oxygenation, thereby reducing the extent of hypoxic injury and decelerating the development of tissue necrosis when administered early after stroke onset. Studies have also demonstrated that low to moderate levels of ethanol not only decrease the risk of stroke, but also reduce post-ischemic sequelae. This article reviews the history of NBO and ethanol therapies, their mechanisms of action, the results of key clinical trials, and the rationale for their use as a combination therapy in the context of stroke treatment.