Given their role in facilitating inflammation, it is not surprising that alcohol-activated microglia have been implicated in alcohol-induced inflammatory pathways. In rats, intermittent and chronic alcohol exposure can activate microglia while concomitantly increasing expression of proinflammatory cytokines and neuronal cell death, providing indirect evidence for the role of microglia in alcohol-induced neuroinflammation and neurotoxicity (Alfonso-Loeches and Guerri 2011; Chastain and Sarkar 2014; Zhao et al. 2013). Alcohol can activate microglia directly, via stimulation of TLRs, or indirectly, via neuronal damage and subsequent release of damage-associated molecular patterns that include HMGB1, resulting in the accumulation of microglia in the brain (i.e., reactive microgliosis) (Alfonso-Loeches and Guerri 2011). Microglial TLR4 seems to be necessary in alcohol-induced activation of microglia and subsequent microglial production of inflammatory mediators and apoptosis of neighboring neurons (Fernandez-Lizarbe et al. 2009, 2013). In an in vitro study (Boyadjieva and Sarkar 2010), microglia-conditioned media enhanced ethanol-induced apoptosis of cultured hypothalamic neurons. Interestingly, the neuronal cell death induced by microglia-conditioned media could be abolished if TNF-α was inactivated in the cultured cells, suggesting that microglial TNF-α production plays a key
