Abstract TP263: The Effect Of Moderate And Excessive Alcohol Exposure On Male Experimental Stroke Outcomes In Mice Is Androgen-Independent

Abstract

Heavy alcohol use is a major stroke risk factor while moderate alcohol use may offer protective benefits. We have shown that moderate ethanol (EtOH) exposure reduces while excessive EtOH exposure increases cortical infarct volume after experimental stroke in male and female mice. The effect of either moderate or excessive EtOH exposure levels in cortex is lost in ovariectomized mice, indicating female sex steroids may be involved in the female response to EtOH exposure and experimental stroke. However, it is unknown if male sex steroids (androgens) might alter the effect of varying EtOH exposure levels on male stroke outcomes. We determined the role of androgens in the male response to EtOH exposure and experimental stroke. Male mice were castrated (CAST) 7-8 days before EtOH exposure and middle cerebral artery occlusion (MCAO) to reduce endogenous androgens. Intact and CAST males were given 0.25 g/kg (moderate dose, n=11) or 2.5 g/kg (excessive dose, n=11) EtOH IP 1 h before 45 min of MCAO. These doses mimic moderate (1-2 drinks daily) or excessive (>4 drinks daily) alcohol use in men based on blood EtOH concentrations. Control male (n=11) and CAST mice (n=10) were given saline (0.015 mL/g) IP 1 h before MCAO. Infarct volume (% contralateral structure) was determined at 72 h reperfusion by analysis of coronal brain slices stained with 2,3,5-triphenyltetrazolium chloride. In contrast to saline treated mice (EtOH vs. saline), acute moderate EtOH exposure reduced (p<0.05) cortical infarct volume in intact (41+3% vs. 54+1%) and CAST (23+5% vs. 34+5%) males. Following acute excessive EtOH exposure, cortical infarct volume was increased (p<0.05) in male (62+2% vs. 54+1%) and CAST (47+4% vs. 34+5%) mice compared to saline treated mice. Clinically, our findings suggest that moderate alcohol use may positively while excessive alcohol use may negatively alter stroke outcomes in men regardless of androgen status. Future studies will need to address the role of androgens in aging male brain as gradual androgen loss during aging (andropause) may not have similar effects on the male brain’s response to EtOH exposure and experimental stroke as an abrupt loss of androgens in CAST mice.