Role of leukocytes in ethanol-induced microvascular injury in the rat brain in situ: potential role in alcohol brain pathology and stroke

Abstract

Effects of acute and chronic alcohol ethanol administration on in vivo microvascular-leukocyte dynamics was studied in brains of naive and leukocyte-depleted rats by direct, quantitative intravital high-resolution TV microscopy, fluorescence microscopy and myeloperoxidase staining. Administration of alcohol produced dose-dependent venular vasospasm, and rolling and adherence of leukocytes to venular walls; leukocyte velocity concomitantly decreased. Intermediate to high doses of ethanol resulted in infiltration of leukocytes and macrophages across venular walls, and concentration-dependent increases in myeloperoxidase staining in parenchyma, and rupture of postcapillary venules with focal hemorrhages. Use of phosphorus 31-nuclear magnetic resonance spectroscopy on intact animals revealed that the latter were associated with whole brain losses in intracellular levels of ATP and phosphocreatine with concomitant rises in intracellular inorganic phosphate and hydrogen ion concentration. Vinblastine-depletion of circulating leukocytes prevented or ameliorated greatly the alcohol-induced microvascular damage and proinflammatory-like reactions. These new results, when viewed in light of other recent findings, suggest that alcohol-induced cerebral vascular and brain damage is dependent, to a large extent, on recruitment of leukocytes.