Introduction: Alcohol consumption has been shown to have both beneficial and detrimental effects on brain function. In the present study, we investigated the potential therapeutic effect of post-stroke ethanol administration and sought to further elucidate the neuroprotective mechanism by assessing its effect on hyperglycolysis and NADPH oxidase activation.
Methods: Sprague-Dawley rats were subjected to middle cerebral artery occlusion for 2 hours. Three sets of experiments were conducted: to demonstrate the neuroprotective effect of ethanol by measuring infarct volume and functional outcome; to determine the effect of ethanol on cerebral glucose uptake and metabolism by measuring both brain and blood glucose concentrations as well as protein expression of glucose transporter 1 and 3, lactate dehydrogenase, phosphofructokinase and lactate; and to determine the effect of ethanol on NADPH oxidase activation by measuring enzymatic activity, protein expression of the catalytic subunit gp91 and NADPH/NADP ratio.
Results: Ethanol treatment (1.5 g/kg) administered immediately upon reperfusion significantly (p<0.05) reduced infarct volume and behavioral dysfunction. Ethanol also significantly (p<0.05) reduced elevations in glycolytic protein expression and lactate levels seen at 3 hours after stroke. Ethanol significantly (p<0.05) increased the reduction in cerebral glucose concentration seen at 3 hours after stroke while significantly (p<0.05) enhancing post-stroke hyperglycemia. Overall, this is indicative of a decrease in cerebral glucose uptake and utilization after ethanol administration. Ethanol also decreased NADPH oxidase activation as evidenced by significant (p<0.05) reductions in enzymatic activity, gp91 expression and NADPH/NADP ratio.
Conclusions: Moderately high dose ethanol (1.5 g/kg) exerts neuroprotection through attenuation of both hyperglycolysis and NADPH activation when administered after stroke. Due to the lack of hypoglycemia associated with ethanol treatment and its selectivity toward decreasing brain glucose uptake and catabolism, its use as a therapeutic modality after onset of ischemia/reperfusion injury, especially in the context of hyperglycemia, seems substantiated.
Patient Care: A better understanding of the mechanisms underlying ethanol-induced neuroprotection will allow a more comprehensive and informed evaluation of ethanol’s clinical potential as a neuroprotectant. The clinical potential of ethanol will be significantly enhanced if it proves to provide salutary effects on post-ischemic cerebral metabolism.
Learning Objectives: By the conclusion of this session, participants should be able to 1) Describe the neuroprotective mechanism of ethanol in terms of its effect on hyperglycolysis and NADPH oxidase activation 2) Discuss, in small groups the potential clinical utility of ethanol in stroke 3) Identify potential obstacles that may preclude the use of ethanol as a clinical therapy