Millions of alcoholics exhibit neuro-cognitive deficits and neuronal injury associated with neuronal degeneration [1-3]. Although oxidative stress and mitochondrial damage are implicated in tissue injury, the underlying mechanisms of alcohol-induced neurological disorders remain elusive. Oxidative stress-induced mitochondrial damage is involved in Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis [4,5]. Increased microglia prior to development of brain atrophy [6], enhanced neuroinflammation, and oxidative damage [7] after chronic ethanol (EtOH) administration in animal models support the putative mechanism for neurodegeneration in alcoholics. Postmortem examination of brain tissues from alcoholics shows cerebral edema, neuronal loss, and blood-brain barrier (BBB) dysfunction [8], associating with the increased risk of hemorrhagic and ischemic stroke among alcoholics [9-11]. We observed that alcohol-induced oxidative stress causes BBB dysfunction [12,13] via an activation of myosin light chain kinase (MLCK) with subsequent phosphorylation of MLC and tight junction proteins [14], activation of inositol 1,4,5-triphosphate receptor-gated intracellular Ca2+ release [15], and activation of matrix metalloproteinases by protein tyrosine kinases [16]. Thus, oxidative stress emerges as the underlying cause of BBB damage, neuroinflammation, and neurological diseases.
