Abstract
BackgroundWe examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption.Methodology/Principal FindingsC57BL/6 J mice were fed a liquid diet without or with 1% alcohol for 8 weeks, orally treated with rosiglitazone (20 mg/kg/day), a peroxisome proliferator-activated receptor gamma (PPARγ)-selective agonist, or GW9662 (3 mg/kg/day), a selective PPARγantagonist, for 2 weeks. The mice were subjected to unilateral middle cerebral artery occlusion (MCAO) for 90 minutes. Brain injury, DNA fragmentation and nuclear PPARγ protein/activity were evaluated at 24 hours of reperfusion. We found that the brain injury and DNA fragmentation were reduced in 1% alcohol-fed mice compared to nonalcohol-fed mice. Rosiglitazone suppressed the brain injury in nonalcohol-fed mice, but didn't alter the brain injury in alcohol-fed mice. In contrast, GW9662 worsened the brain injury in alcohol-fed mice, but didn't alter the brain injury in nonalcohol-fed mice. Nuclear PPARγ protein/activity at peri-infarct and the contralateral corresponding areas of the parietal cortex was greater in alcohol-fed mice compared to nonalcohol-fed mice. Using differentiated catecholaminergic (CATH.a) neurons, we measured dose-related influences of chronic alcohol exposure on nuclear PPARγ protein/activity and the influence of low-dose alcohol exposure on 2-hour oxygen-glucose deprivation (OGD)/24-hour reoxygenation-induced apoptosis. We found that low-dose alcohol exposure increased nuclear PPARγ protein/activity and protected against the OGD/reoxygenation-induced apoptosis. The beneficial effect of low-dose alcohol exposure on OGD/reoxygenation-induced apoptosis was abolished by GW9662.Conclusions/SignificanceOur findings suggest that chronic consumption of low-dose alcohol protects the brain against I/R injury. The neuroprotective effect of low-dose alcohol consumption may be related to an upregulated PPARγ.
Highlights
Ischemic stroke is one of the leading causes of death and permanent disability and has limited therapeutic options
middle cerebral artery occlusion (MCAO)/reperfusion-induced brain injury After the mice were fed with nonalcohol or 1% alcohol diets for 8 weeks and treated with rosiglitazone or GW9662 for 2 weeks, they were subjected to unilateral MCAO for 90 minutes
Treatment with peroxisome proliferator-activated receptor gamma (PPARc)-selective antagonist abolished the protective effect of low-dose alcohol on transient focal cerebral ischemia-induced brain injury and oxygen-glucose deprivation (OGD)/reoxygenation-induced apoptosis
Summary
Ischemic stroke is one of the leading causes of death and permanent disability and has limited therapeutic options. Increasing evidence suggests that light-moderate alcohol exposure can typically initiate cytoprotective mechanisms [1]. Epidemiological studies suggest that light-moderate alcohol consumption reduces mortality and infarct volume from ischemic stroke [2,3]. A prospective cohort study in men found a beneficial effect of light alcohol consumption on functional outcome from ischemic stroke [4]. These epidemiological studies didn’t provide detailed information according to ischemic stroke subtype, ischemic duration and ischemic region. Mechanisms underlying neuroprotective effect of light-moderate alcohol consumption are not clear. We examined the influence of low-dose alcohol consumption on cerebral ischemia/reperfusion (I/R) injury in mice and a potential mechanism underlying the neuroprotective effect of low-dose alcohol consumption
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