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.
Keywords: Blood brain barrier, combination therapy, ethanol, ischemia, neuroprotection, normobaric oxygen therapy, oxidative
stress, reperfusion, stroke.
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