Journal of neuroscience research
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Pyruvate dehydrogenase complex (PDH) is a brain mitochondrial matrix enzyme. PDH impairment after stroke is particularly devastating given PDH's critical role in the link between anaerobic and aerobic metabolism. This study evaluates the restoration of oxidative metabolism and energy regulation with a therapeutic combination of normobaric oxygen (NBO) plus either therapeutic hypothermia (TH) or ethanol. ⋯ Compared with the monotherapeutic approaches, the combined therapies provided the most significant declines in ROS generation. Reperfusion with t-PA followed by 60% NBO improves the efficacy of EtOH or TH in neuroprotection by ameliorating oxidative injury and improving PDH regulation. Comparable neuroprotective effects were found when treating with either EtOH or TH, suggesting a similar mechanism of neuroprotection and the possibility of substituting EtOH for TH in clinical settings. © 2016 Wiley Periodicals, Inc.