PYRROLIDINE DITHIOCARBAMATE ATTENUATES ALCOHOL-INDUCED LEUKOCYTE-ENDOTHELIAL CELL-INTERACTION AND CEREBRAL VASCULAR DAMAGE IN RATS - POSSIBLE ROLE OF ACTIVATION OF TRANSCRIPTION FACTOR NF-KAPPA-B IN ALCOHOL BRAIN PATHOLOGY

Effects of chronic (14-day) pretreatment of orally administered pyrrol idine dithiocarbamate (PDTC) (100 or 200 mg/kg/day) on alcohol-induced venular cerebrovasospasm, microvessel rupture, leukocyte-endothelial chemoattraction, and microhemorrhaging was studied by direct, quantita tive in vivo high-resolution TV microscopy of the intact rat brain. Sh am animals chronically treated with placebo exhibited concentration-de pendent venular cerebrovasospasm, endothelial-leukocyte rolling and at traction, microvessel rupture, and focal hemorrhages, irrespective of route (i.e., perivascular, systemic) of ethanol adminstration. PDTC pr etreatment either prevented or ameliorated greately the cerebrovasospa sm, leukocyte-endothelial chemoattraction, and brain-vascular damage i nduced by ethanol. These new data suggest that alcohol induces cerebra l vascular and brain damage by reperfusion injury events, which trigge r induction of proinflammatory factors, and transcription factor NF-ka ppa B 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 cereb ral ischemia and stroke. (C) 1998 Elsevier Science Inc.