Beneficial effect on nebracetam on energy metabolism after microsphere-induced embolism in rat brain.

S Takeo, K Miyake, K Tanonaka, N Takagi, K Takagi, K Kishimoto, M Suzuki, A Katsuragi, M Goto, S Oshikawa
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Abstract

The present study was undertaken to examine the possible therapeutic effects on nebracetam on the energy metabolism of rat brain regions in microsphere-induced, sustained ischemia. Microsphere embolism was induced by injection of 900 microspheres (48 microns in diameter) into the right internal carotid artery of rats, and changes in the energy metabolism of the cerebral cortex, striatum and hippocampus of the right hemisphere were determined without and with nebracetam treatment. Microsphere embolism induced increases in lactate and glucose contents and decreases of ATP and creatine phosphate contents in these regions, suggesting that sustained impairment of cerebral energy metabolism occurred. These changes were gradually reversed with time after the operation. Treatment of microsphere-injected rats with 30 mg/kg of nebracetam, p.o., twice a day, was started one day after the onset of cerebral ischemia. The effects of treatment with nebracetam on cerebral energy metabolites were determined on the 3rd and 7th day after operation. Treatment of microsphere-injected rats with nebracetam significantly improved these variables on the 3rd day after the onset of ischemia, but the improvement was small on the 7th day, except for reversal of the hippocampal ATP content. These results suggest that nebracetam is a possible therapeutic agent for the restoration of cerebral energy metabolism against microsphere-induced, sustained cerebral ischemia.

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纳布西坦对大鼠脑微球栓塞后能量代谢的有益影响。
本研究旨在探讨纳布西坦对微球诱导的持续缺血大鼠脑区能量代谢的可能治疗作用。将直径为48微米的900个微球注入大鼠右侧颈内动脉,观察纳布西坦处理前后大鼠右半球大脑皮层、纹状体和海马能量代谢的变化。微球栓塞导致这些区域乳酸和葡萄糖含量升高,ATP和磷酸肌酸含量降低,提示发生了持续的脑能代谢损伤。这些变化随着手术后时间的推移而逐渐逆转。大鼠脑缺血后1天开始微球注射纳布西坦30 mg/kg, p.o.,每日2次。术后第3、7天观察纳布西坦治疗对脑能代谢产物的影响。微球注射纳布西坦在缺血后第3天显著改善了这些指标,但在第7天,除了海马ATP含量逆转外,改善幅度很小。这些结果表明,纳布西坦可能是一种治疗微球诱导的持续性脑缺血的恢复脑能代谢的药物。
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