Cerebral cortical cholesterol changes in cobalt-induced epilepsy.
The present study was designed to elucidate cerebral cortical cholesterol changes observed earlier in cobalt-induced epilepsy in the rat. This model is produced by insertion of cobalt metal rods into the cerebral cortex. Seven days after implantations of cobalt (or other metals), measurements of cerebral cortical lipid concentrations were made in the direct area of metal implantation (lesion area) and in the nonnecrotic tissue immediately adjacent to the lesion site (adjacent area). The cortical concentration of free cholesterol decreased and the concentrations of cholesterol esters (CE) greatly increased in the adjacent area of rats implanted with epileptogenic metals (cobalt and nickel) but not in those implanted with nonepileptogenic metals (copper and stainless steel). Differences in the fatty acid compositions of CE from plasma and those from cobalt-lesioned cortex indicated that the accumulated CE originated in the brain rather than from the plasma CE pool. A time course study revealed that changes in the cortical concentrations of free and esterified cholesterol precedes the first appearance of epileptiform activity as measured by electrocorticography. The reduction of free cholesterol levels most likely reflects increased cholesterol metabolism in the cobalt-lesioned cortex. A major portion of this free cholesterol appears to be converted to CE, but not to bile acid or neutral sterol (potential products of cholesterol metabolism). The concentration of free fatty acids, the other substrate of CE formation, was decreased in the lesion site. The increased metabolism of cholesterol could not be explained by changes in the activities of CE synthetase and hydrolase(s). Since cholesterol in the brain is found almost exclusively in membranes, it is likely that these sterol changes reflect membrane alterations or disintegration. However, the exact relationship of these changes to the epileptogenic effect of cobalt remains unclear.
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D002540:Cerebral Cortex / Q000032:analysis* / Q000201:enzymology; D002784:Cholesterol / Q000032:analysis*; D002788:Cholesterol Esters / Q000032:analysis; D003035:Cobalt; D005227:Fatty Acids / Q000032:analysis; D008297:Male; D051381:Rats; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism
D002788:Cholesterol Esters; D005227:Fatty Acids; D003035:Cobalt; D002784:Cholesterol; D000217:Acyltransferases; D002787:Sterol Esterase