Ethanol and adult CNS neurodamage: oxidative stress, but possibly not excitotoxicity.
Evidence from experiments with adult rodents chronically treated with ethanol via either repetitive binges or continuous intake/exposure supports the occurrence of brain oxidative stress and, at least in binge intoxication/rat models, its essential causative role in neurodamage. However, pharmacological antagonism experiments reveal that N-methyl-D-aspartate (NMDA) receptor-dependent excitotoxicity is not responsible for adult mammalian brain neurodegeneration caused by repetitive binge ethanol intoxication and withdrawals. Since NMDA receptor antagonists apparently are untested with respect to neuronal death/loss in continuous intake/ingestion rodent models, e.g., ethanol/water or ethanol/liquid diets, it is therefore erroneous to assert, as is often done, that excitotoxicity is an important mechanism for ethanol-induced adult mammalian brain damage. Alternatively, results from several laboratories indicate that neurodegeneration due to chronic binge ethanol exposure/withdrawal may be dependent on redox transcription factor signaling and neuroinflammatory/oxidative stress pathways (increased arachidonic acid mobilization and pro-inflammatory cytokines; decreased anti-inflammatory cytokines) downstream of microglial/astroglial activation and moderate yet significant brain edema.
Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA. mcollin@lumc.edu
Michael A
MA
Collins
Edward J
EJ
Neafsey
D000328:Adult; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol