Microglia are the innate immune cells of brain and are known to initiate neuroinflammatory responses [6]. Iba1 + IR provides a morphological assessment of microglial activation that parallels the progressive proinflammatory oxidative stress responses in brain to ethanol, poly I:C and ethanol-poly I:C (Figures 4 and 5). Minocycline, an antibiotic known to block microglial activation [43], was used to investigate the link between proinflammatory microglial activation and markers of neuronal death. Minocycline treatment blocked ethanol-poly I:C-induced increases in microglial Iba1 + IR (Figure 11) as well as caspase-3 + IR (Figure 12) suggesting microglial proinflammatory activation contributes to neuronal death. Recent studies have found that the opiate receptor antagonist naltrexone has anti-inflammatory actions that, in part, are related to binding to TLR receptors [44,45]. We found that naltrexone blocked ethanol-poly I:C increased microglial activation and expression of activated caspase-3, a cell death marker (Figures 11 and 12). These findings indicate that minocycline and naltrexone inhibition of microglial activation by ethanol, poly I:C and ethanol pretreatment potentiated proinflammatory responses blunt ethanol-poly I:C potentiated neurodegeneration.
