Excitotoxicity and Alcohol‐Related Brain Damage

Abstract

Hyperexcitability following chronic alcohol exposure appears to result in enhanced activation of glutamatergic synapses in the brain. This enhanced glutamatergic transmission probably results from a combination of increased NMDA receptor activation, decreased GABAA receptor activation and increased function of voltage-activated calcium channels. Prolonged or repetitive bouts of enhanced excitatory transmission during withdrawal may destroy central neurons via "excitotoxic" mechanisms. Increased NMDA receptor activation might initiate toxicity by increasing intracellular calcium. Summation of these effects with increased intracellular calcium from voltage-activated channels might promote disinhibition and enhance cellular damage. Recent studies suggest that NMDA receptor-initiated excitotoxicity may result from thiamine deficiency. Alterations in neurotransmitter levels and receptor function during alcohol-related thiamine deficiency may contribute to this neuropathology. Thus, excitotoxic damage due to neural compensation for sustained alcohol levels and nutritional deficits may underlie aspects of alcohol-related brain damage.