Cerebral ischemic preconditioning reduces glutamate excitotoxicity by up-regulating the uptake activity of GLT-1 in rats
Cerebral ischemic preconditioning reduces glutamate excitotoxicity by up-regulating the uptake activity of GLT-1 in rats
复制标题
脑缺血预处理通过上调大鼠 GLT-1 的摄取活性降低谷氨酸兴奋毒性
DOI：
10.1007/s00726-014-1723-1
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发表时间：
2014-06-01
期刊：
影响因子：
3.5
通讯作者：
Li, Wenbin
中科院分区：
文献类型：
--
作者：
Gong, Jianxue;Gong, Shujuan;Li, Wenbin
我们先前的研究表明，脑缺血预适应(CIP)可上调大鼠脑缺血耐受诱导过程中胶质细胞谷氨酸转运体-1(GLT-1)的表达。本研究通过脑微透析和高效液相色谱法观察细胞外谷氨酸浓度的变化，进一步探讨GLT-1在此过程中的摄取活性。结果表明，致死性脑缺血后，海马区谷氨酸浓度明显升高，达到基础水平的7倍，这与CA1区神经元迟发性死亡有关。致死性脑缺血损伤前2天给予CIP保护锥体神经元延迟性死亡，谷氨酸浓度峰值降至基础水平的3.9倍。此外，预先给予GLT-1的抑制剂二氢海人酸能阻止CIP对缺血诱导的CA1细胞死亡的保护作用。同时，与CIP+脑缺血组相比，谷氨酸浓度峰值明显升高，达到基础水平的6倍。这些结果表明，CIP通过上调谷氨酸摄取GLT-1的活性，从而降低谷氨酸的兴奋性毒性，从而诱导脑缺血耐受。
Our previous study has shown that cerebral ischemic preconditioning (CIP) can up-regulate the expression of glial glutamate transporter-1 (GLT-1) during the induction of brain ischemic tolerance in rats. The present study was undertaken to further explore the uptake activity of GLT-1 in the process by observing the changes in the concentration of extracellular glutamate with cerebral microdialysis and high-performance liquid chromatography. The results showed that a significant pulse of glutamate concentration reached the peak value of sevenfold of the basal level after lethal ischemic insult, which was associated with delayed neuronal death in the CA1 hippocampus. When the rats were pretreated 2 days before the lethal ischemic insult with CIP which protected the pyramidal neurons against delayed neuronal death, the peak value of glutamate concentration decreased to 3.9 fold of the basal level. Furthermore, pre-administration of dihydrokainate, an inhibitor of GLT-1, prevented the protective effect of CIP on ischemia-induced CA1 cell death. At the same time, compared with the CIP + Ischemia group, the peak value of glutamate concentration significantly increased and reached sixfold of the basal level. These results indicate that CIP induced brain ischemic tolerance via up-regulating GLT-1 uptake activity for glutamate and then decreasing the excitotoxicity of glutamate.