Influences of Ethanol on Inflammation and Apoptosis Following Transient Focal Cerebral Ischemia

Abstract

BackgroundInflammation and apoptosis are two key elements involved in cerebral ischemia/reperfusion (I/R) injury. Ethanol is one of the most commonly and regularly used chemical substances. We determined the influences of chronic ethanol consumption on inflammation and apoptosis following transient focal cerebral ischemia.MethodsMale C57/BL6J mice were divided into 6 groups and gavage fed with 0.175, 0.35, 0.7, 1.4, 2.8 g/kg/d ethanol or volume‐matched water once a day for eight weeks. Cerebral I/R injury, adhesion molecules, microglial activation, neutrophil infiltration, pro‐ and anti‐inflammatory cytokines/chemokines, MMPs, cleaved caspase‐3‐positive neurons, and TUNEL‐positive neurons were evaluated at 24 hours after a 90‐minute unilateral middle cerebral artery occlusion (MCAO).ResultsCerebral I/R injury was only significantly reduced in 0.7 g/kg/d ethanol group (peak blood ethanol concentration: 9 mM) and increased in 2.8 g/kg/d ethanol group (peak blood ethanol concentration: 37 mM). Baseline and post‐ischemic upregulation of ICAM‐1 and E‐selectin were suppressed in all ethanol groups. Post‐ischemic microglial activation and neutrophil infiltration were significantly alleviated in 0.175–1.4 g/kg/d ethanol groups but dramatically exacerbated in 2.8 g/kg/d ethanol group. Ethanol tends to dose‐dependently increase both baseline pro‐ and anti‐inflammatory cytokines/chemokines, but dose‐dependently suppressed post‐ischemic increase in pro‐inflammatory cytokines/chemokines. Surprisingly, 2.8 g/kg/d ethanol strengthened post‐ischemic increase in anti‐inflammatory cytokines/chemokines. Furthermore, although baseline MMP‐9 activity was reduced in 0.7 g/kg/d ethanol group, the magnitude of post‐ischemic increase in MMP‐9 activity was significantly less in 2.8 g/kg/d ethanol group. Both cleaved caspase‐3‐positive neurons and TUNEL‐positive neurons were significantly less in 0.7 g/kg/d ethanol group.ConclusionsLight alcohol consumption protects against cerebral I/R injury by suppressing post‐ischemic inflammation and apoptosis, whereas heavy alcohol consumption may exacerbate cerebral I/R injury via an inflammation‐ and apoptosis‐independent mechanism.Support or Funding InformationThis study was supported by a National Institutes of Health Grant (AA023610) and funds from Louisiana State University Health Sciences Center‐Shreveport to HS, a postdoctoral fellowship to CL and a predoctoral fellowship to KDM from the Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Science Center‐Shreveport.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.