Department of Pathophysiology, Hebei Medical University, 361 Zhongshan East Road, Shijiazhuang, 050017, People's Republic of China.
Amino Acids. 2014 Jun;46(6):1537-45. doi: 10.1007/s00726-014-1723-1. Epub 2014 Mar 19.
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.
我们之前的研究表明，脑缺血预处理（CIP）可以在诱导大鼠脑缺血耐受期间上调胶质谷氨酸转运体-1（GLT-1）的表达。本研究旨在通过脑微透析和高效液相色谱观察细胞外谷氨酸浓度的变化，进一步探讨 GLT-1 在这一过程中的摄取活性。结果表明，在致死性缺血损伤后，谷氨酸浓度会出现显著的脉冲，达到基础水平的七倍峰值，这与 CA1 海马区神经元延迟性死亡有关。当大鼠在致死性缺血损伤前 2 天进行 CIP 预处理时，可保护锥体神经元免受神经元延迟性死亡的影响，谷氨酸浓度峰值下降至基础水平的 3.9 倍。此外，预先给予 GLT-1 抑制剂二氢克尿噻可阻止 CIP 对缺血诱导的 CA1 细胞死亡的保护作用。同时，与 CIP+缺血组相比，谷氨酸浓度峰值显著增加，达到基础水平的 6 倍。这些结果表明，CIP 通过上调 GLT-1 对谷氨酸的摄取活性，从而降低谷氨酸的兴奋性毒性，诱导脑缺血耐受。
