Figure 1. Effects of chronic alcohol activation of pro-inflammatory signaling in the brain.

(Top left) In a “healthy” brain, neurons, astrocytes, and microglia release growth signals (i.e., trophic factors such as brain-derived neurotrophic factor [blue dots]) supporting neuronal and glial functions. (Top right) With chronic binge alcohol exposure, all cells show changes, such as reductions in soma and synapses. Other changes include increased high mobility group box protein 1 (HMGB1) release (orange dots) in neurons, hyper-ramification and pro-inflammatory activation of microglia, and activation of astrocytes. (Bottom) Without alcohol exposure, transcription of growth factors, such as brain-derived neurotrophic factor, is high, providing trophic support. In a brain exposed to chronic binge drinking, cellular transcription shifts, with increasing pro-inflammatory transcripts. Note: Not shown are other pro-inflammatory signals, although pro-inflammatory changes in transcription likely involve multiple signals; all brain cell types are proposed to change cellular transcriptomes and subtypes.