Chunk #28 — Mechanisms of Neurodegeneration Related to Alcohol’s Effects on Neuroimmune Signaling in the Brain — Role of Hyperexcitability and Excitotoxicty
As indicated above, ethanol causes HMGB1 release, creating hyperexcitability that disrupts synaptic plasticity and sensitizes to excitotoxicity. HMGB1 is massively released during brain damage, resulting in persistent neuroimmune-gene induction (Kim et al. 2006). Maroso and colleagues (2010) found that increased HMGB1 release was associated with hippocampal excitability that caused seizures, leading to persistent increases in HMGB1 and excitability. Ethanol has modest cumulative effects with repeated chronic exposure, further exacerbating excitability and excitotoxicity resulting from increased neuroimmune signaling. Thus, the global neurodegeneration associated with alcoholism, with the most severe losses observed in the frontal cortex, is secondary to the persistent and progressive neuroimmune activation.
