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Chunk #29 — Discussion

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Chronic alcohol-induced neuroinflammation involves CCR2/5-dependent peripheral macrophage infiltration and microglia alterations.
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Previous research has described neuroinflammation associated with chronic alcohol consumption. We hypothesized that alcohol could induce macrophage infiltration into the brain and that this infiltration could drive the neuroinflammation observed after chronic alcohol. We therefore tested if blockade using a CCR2/5 dual inhibitor of the chemokine network associated with macrophage chemoattraction could reduce alcohol-induced neuroinflammation. Here, we show that chronic alcohol induces region-specific infiltration of IMs into the CNS that is associated with cytokine expression and microglial activation. Inhibition of CCR2/5 signaling using the small molecule inhibitor CVC abrogated the infiltration of macrophages, reduced cytokine expression, and partially normalized microglial morphology.