Pyrrolidine dithiocarbamate attenuates alcohol-induced leukocyte-endothelial cell interaction and cerebral vascular damage in rats: possible role of activation of transcription factor NF-kappaB in alcohol brain pathology.

Effects of chronic (14-day) pretreatment of orally administered pyrrolidine dithiocarbamate (PDTC) (100 or 200 mg/kg/day) on alcohol-induced venular cerebrovasospasm, microvessel rupture, leukocyte-endothelial chemoattraction, and microhemorrhaging was studied by direct, quantitative in vivo high-resolution TV microscopy of the intact rat brain. Sham animals chronically treated with placebo exhibited concentration-dependent venular cerebrovasospasm, endothelial-leukocyte rolling and attraction, microvessel rupture. and focal hemorrhages, irrespective of route (i.e., perivascular, systemic) of ethanol administration. PDTC pretreatment either prevented or ameliorated greatly the cerebrovasospasm, leukocyte-endothelial chemoattraction, and brain vascular damage induced by ethanol. These new data suggest that alcohol induces cerebral vascular and brain damage by reperfusion injury events, which trigger induction of proinflammatory factors, and transcription factor NF-kappaB and lipid peroxidation of vascular smooth muscle and endothelial cell membranes; these proinflammatory, pro-oxidant, and redox events could play a crucial role in the pathogenesis of alcohol-induced cerebral ischemia and stroke.