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. 2006 Apr 5;14(4):365–371. doi: 10.1111/j.1750-3639.2004.tb00079.x

Chronic Ethanol Treatment Enhances Inflammatory Mediators and Cell Death in the Brain and in Astrocytes

Soraya L Vallés 1,*, Ana M Blanco 1,*, María Pascual 1, Consuelo Guerri 1,✉
PMCID: PMC8095743  PMID: 15605983

Abstract

Inflammatory processes and cytokine expression have been implicated in the pathogenesis of several neurodegenerative disorders. Chronic ethanol intake induces brain damage, although the mechanisms involved in this effect are not well understood.

We tested the hypothesis that activation of glial cells by ethanol would induce stimulation of signaling pathways and inflammatory mediators in brain, and would cause neurotoxicity. We used cerebral cortex from control and chronic ethanol‐fed rats, which received ethanol‐liquid diet for 5 months and cultured of astrocytes exposed to 75 mM ethanol for 7 days. Our results demonstrate that chronic ethanol treatment up‐regulates iNOS, COX‐2 and IL‐1β in rat cerebral cortex and in cultured astrocytes.

Under both experimental conditions, up‐regulation of these inflammatory mediators and IL‐1 RI concomitantly occurs with the stimulation of IRAK and MAP kinases, including ERK1/2, p‐38 and JNK, which trigger the downstream activation of oxidant‐sensitive transcription factors NF‐kB and AP‐1. These effects were associated with an increased in both caspase‐3 and apoptosis in ethanol‐fed rats and in astrocytes exposed to ethanol. In conclusion, chronic ethanol treatment stimulates glial cells, upregulating the production and the expression of inflammatory mediators in the brain, and activating signalling pathways and transcription factors involved in inflammatory damage and cell death.

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