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沙土鼠全脑缺血诱导的纹状体、海马和大脑皮质氨基酸水平的改变

Alterations of amino acid levels from striatum, hippocampus, and cerebral cortex induced by global cerebral ischemia in gerbil.

作者信息

Tang X C, Rao M R, Hu G, Wang H

机构信息

Department of Physiology and Pharmacology, Nanjing Medical University, Nanjing 210029, China.

出版信息

Acta Pharmacol Sin. 2000 Sep;21(9):819-23.

Abstract

AIM

To investigate global cerebral ischemia-induced alterations in the levels of glutamate, aspartate, gamma-aminobutyric acid (GABA), glutamine, glycine, and taurine from hippocampus, striatum, and cerebral cortex in gerbils.

METHODS

The gerbil global cerebral ischemia model was prepared by bilateral carotid artery occlusion; the contents of amino acids were assayed using high performance liquid chromatography (HPLC) combined with fluorescent detection after precolumn derivatization.

RESULTS

After the ligation of bilateral carotid artery for 5 min and reperfusion for 60 min, the contents of glutamate from hippocampus, striatum, and cortex in gerbils were increased by 40%, 49%, and 67%, respectively. Similarly, the global cerebral ischemia resulted in increase by 80%, 69%, and 83% of aspartate contents in hippocampus, striatum, and cortex, respectively. Moreover, the same treatment also induced significant increases in the contents of GABA, glutamine, glycine, and taurine from various brain regions in gerbils. Furthermore, pretreatment with ketamine (120 mg/kg, i.p.) reversed ischemia-evoked increases of glutamate, aspartate, glycine, and glutamine in hippocampus, striatum, and cortex of gerbils. However, administration of ketamine (120 mg/kg, i.p.) markedly suppressed but not abolished the ischemia-induced increases of taurine and GABA from hippocampus, striatum, and cortex in gerbils.

CONCLUSION

The increases of glutamate, aspartate, glycine, and glutamine induced by acute global cerebral ischemia may constitute the biochemical basis of ischemic brain damage. Correspondingly, the release of GABA and taurine may be an important self-protective mechanism. Ketamine may protect neurons against ischemic insult by inhibiting global cerebral ischemia-evoked increase of glutamate, glycine, and aspartate.

摘要

目的

研究沙土鼠全脑缺血后海马、纹状体和大脑皮质中谷氨酸、天冬氨酸、γ-氨基丁酸(GABA)、谷氨酰胺、甘氨酸和牛磺酸水平的变化。

方法

采用双侧颈总动脉闭塞法制备沙土鼠全脑缺血模型;采用高效液相色谱(HPLC)结合柱前衍生荧光检测法测定氨基酸含量。

结果

双侧颈总动脉结扎5分钟并再灌注60分钟后,沙土鼠海马、纹状体和皮质中谷氨酸含量分别增加了40%、49%和67%。同样,全脑缺血导致海马、纹状体和皮质中天冬氨酸含量分别增加80%、69%和83%。此外,相同处理还导致沙土鼠各脑区中GABA、谷氨酰胺、甘氨酸和牛磺酸含量显著增加。此外,氯胺酮(120mg/kg,腹腔注射)预处理可逆转沙土鼠海马、纹状体和皮质中缺血诱发的谷氨酸、天冬氨酸、甘氨酸和谷氨酰胺增加。然而,氯胺酮(120mg/kg,腹腔注射)给药可显著抑制但不能消除沙土鼠海马、纹状体和皮质中缺血诱导的牛磺酸和GABA增加。

结论

急性全脑缺血诱导的谷氨酸、天冬氨酸、甘氨酸和谷氨酰胺增加可能构成缺血性脑损伤的生化基础。相应地,GABA和牛磺酸的释放可能是一种重要的自我保护机制。氯胺酮可能通过抑制全脑缺血诱发的谷氨酸、甘氨酸和天冬氨酸增加来保护神经元免受缺血性损伤。

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