Bierkamper G G, Cenedella R J
Epilepsia. 1978 Apr;19(2):155-67. doi: 10.1111/j.1528-1157.1978.tb05026.x.
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.
本研究旨在阐明大鼠钴诱导癫痫早期观察到的大脑皮质胆固醇变化。该模型是通过将金属钴棒插入大脑皮质产生的。植入钴（或其他金属）7天后，在金属植入的直接区域（损伤区域）和紧邻损伤部位的非坏死组织（相邻区域）测量大脑皮质脂质浓度。植入致痫金属（钴和镍）的大鼠相邻区域游离胆固醇浓度降低，胆固醇酯（CE）浓度大幅升高，而植入非致痫金属（铜和不锈钢）的大鼠则未出现这种情况。血浆CE和钴损伤皮质CE的脂肪酸组成差异表明，积累的CE起源于大脑而非血浆CE池。一项时间进程研究表明，通过脑电图测量，游离和酯化胆固醇的皮质浓度变化先于癫痫样活动的首次出现。游离胆固醇水平的降低很可能反映了钴损伤皮质中胆固醇代谢的增加。这种游离胆固醇的很大一部分似乎转化为CE，但未转化为胆汁酸或中性固醇（胆固醇代谢的潜在产物）。损伤部位游离脂肪酸（CE形成的另一种底物）浓度降低。胆固醇代谢增加无法用CE合成酶和水解酶活性的变化来解释。由于大脑中的胆固醇几乎只存在于细胞膜中，这些固醇变化很可能反映了膜的改变或解体。然而，这些变化与钴致痫作用的确切关系仍不清楚。
