Primed in Great Britain Pergamon Press pic Medical Council on Alcoholism THE GENESIS OF ALCOHOLIC BRAIN TISSUE INJURY

Abstract — 1. Acetaldehyde has been implicated in the pathogenesis of alcohol-related liver damage by two mechanisms. Adduct formation with many tissue constituents, especially proteins, makes them immunologically foreign or reduces enzyme activity and formation of cytotoxic free radicals from acetaidehyde metabolism. Adduct formation damage to microtubule associated proteins and to hepatocyte membranes impedes protein movement into, out of and around the cell. 2. Evidence that these mechanisms also have a role in alcoholic brain damage includes raised blood acetaldehyde in alcoholics, especially in those chemically dependent, or in other abnormal states; effects of extra-hepatic free radical toxicity, including induction of superoxide dismutase activity and damaged, abnormal variants of the thiamin-dependent enzyme transketolase and extrahepatic acetaldehyde-adduct formation with haemoglobin. That acetaldehyde-mediated impairment of microtubule systems also damages the brain is suggested by its importance for the maintenance by protein transport of often greatly extended brain cell processes. 3. Oxygen-derived free radicals can damage brain tissue, the effects including cerebral oedema, neuronal loss and damage to the blood-brain barrier, all changes also reported in th