Effects of extracellular pressure and alcohol on the microglial response to inflammatory stimulation

Abstract

TBI induces a neuroinflammatory response frequently associated with increased intracranial pressure (ICP). We investigated the effects of alcohol and increased extracellular pressure on murine BV-2 microglial proliferation and cytokine responses to lipopolysaccharide (LPS) stimulation. BV-2 cells were cultured under 0 or 30mmHg increased extracellular pressure without or with ethanol (100mM) or LPS (10ng/ml) for 24 hours. We assessed cell proliferation via MTS assay and secretion of the pro-inflammatory cytokines TNF-α, IL-6, and MCP-1 by ELISA. Increased pressure and LPS stimulation each promoted proliferation. Ethanol pretreatment blocked these effects. Basal TNF-α and IL-6 secretion were at the limits of delectability. Basal MCP-1 production was stimulated by pressure, which was blocked by ethanol. Even this low LPS dose stimulated microglial secretion of TNF-α, IL-6 and MCP-1. Pressure inhibited LPS-stimulated production of these proinflammatory cytokines, while ethanol pretreatment blocked LPS-stimulated cytokine production. The combination of pressure and ethanol further reduced TNF-α, IL-6 and MCP-1 secretion by LPS-stimulated microglial cells. Alcohol’s anti-inflammatory effects may contribute to the reduced TBI mortality that some have described in acutely intoxicated patients, while pressure downregulation of inflammatory cytokine release could create a negative feedback that ameliorates inflammation in TBI.

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Adoptive transfer of T regulatory cells inhibits lipopolysaccharide‐induced inflammation in fetal brain tissue in a late‐pregnancy preterm birth mouse model

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Expression of CCL2 and CCR2 in the hippocampus and the interventional roles of propofol in rat cerebral ischemia/reperfusion

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