Inflammatory Effects of Chronic Ethanol Exposure and Interactions with Cannabinoids and Spinal Cord Injury

摘要

Alcohol consumption leads to a number of disorders most notably ALD, alcoholism, and inflammation. The present study aimed to investigate the effects of a Lieber-DeCarli chronic-plus-single-binge alcohol model on animal withdrawal behaviors to 1) to determine if this model manifests any symptoms of withdrawal and 2) how severely the symptoms are expressed. To evaluate alcohol's effect(s), a variety of behavioral assays were performed, and several of the tests exhibited signs of increased withdrawal-like behavior in ethanol exposed mice, most notably showing anxiety and convulsion-like behaviors.;Inflammation is one of the main hallmarks of alcohol associated diseases and pathologies. Two of the main organs affected by alcohol induced inflammation are the brain and the liver; both of which have been shown to be structurally and physiologically disturbed by chronic alcohol consumption. Two compounds from the cannabis plant, cannabidiol and beta-caryophyllene have been isolated and shown to have anti- inflammatory properties. The potential anti-inflammatory effects of both compounds separately and in combination were assessed against ethanol exposure using a chronic- plus-single-binge alcohol model using a Lieber-DeCarli liquid diet. Immunofluorescence analysis of brain microglia and liver Kupffer cells was used to evaluate the inflammatory profile affected by alcohol and by treatment with cannabinoids. A second cohort of mice exposed to ethanol and administered CBD, BCP or both cannabinoids together was used to investigate if these compounds had effects on inflammatory cytokine concentrations or accumulation of fat in the liver. Luminex assays were used for analysis of specific cytokines in the serum and oil red o staining was used to see the potential effect on fat accumulation.;Spinal cord injury results in a massive secondary inflammatory reaction that can compound on the already physically damaged tissue. Ethanol is known to induce inflammation when consumed acutely and chronically. To assess the effect of ethanol consumption on spinal cord injury we investigate pain sensitivity, motor and sensory recovery as well as the size of the lesion at the site of impact on the spinal cord. To examine motor recovery, we use a Basso Mouse Scale (BMS) for locomotion which assesses the mouse's ability to move various parts of their hind limbs and overall coordination. Lesion size is measured using a previously characterized eriochrome cyanine with cresyl violet counterstain that elucidates damaged areas of the spinal cord in both the white and grey matter. Additionally, the glial profile was observed and quantified using a GFAP immunofluorescence stain. Interestingly, mice given ethanol had improved BMS scores when compared to control diet counterparts. Furthermore, lesion size and glial profile were also reduced in ethanol animals, showing that ethanol can have a protective, immune-suppressive effect when consumed after injury, thereby limiting secondary insult that results from SCI.