Ceftriaxone modulates uptake activity of glial glutamate transporter-1 against global brain ischemia in rats
Ceftriaxone modulates uptake activity of glial glutamate transporter-1 against global brain ischemia in rats
复制标题
头孢曲松调节神经胶质谷氨酸转运蛋白 1 的摄取活性以对抗大鼠全脑缺血
DOI：
10.1111/jnc.12958
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发表时间：
2015-01-01
影响因子：
4.7
通讯作者：
Li, Wen-Bin
中科院分区：
文献类型：
--
作者：
Hu, Yu-Yan;Xu, Jing;Li, Wen-Bin
头孢曲松(CEF)选择性增加神经胶质谷氨酸转运体-1(GLT-1)的表达，在某些情况下被认为具有神经保护作用。然而，CEF对GLT-1谷氨酸摄取的影响主要是通过体外研究，如原代神经元/星形胶质细胞培养或脑片。此外，CEF对不同缺血模型神经元的作用仍有差异。因此，本研究旨在观察CEF对大鼠全脑缺血时神经元的影响，特别是为CEF上调谷氨酸摄取GLT-1对神经元的保护作用提供直接证据。神经病理学评估表明，给予CEF，特别是预治疗方案，可显著防止通常由全脑缺血所致的海马CA1区迟发性神经元死亡。同时，预先给予CEF可显著上调GLT-1的表达。特别是成年大鼠活体细胞的~3H-谷氨酸摄取GLT-1实验表明，谷氨酸摄取上调伴随着GLT-1表达的上调。用反义寡核苷酸或二氢海人藻酸盐抑制GLT-1可显著抑制CEF诱导的GLT-1摄取上调和抗全脑缺血的神经保护作用。因此，我们可以得出结论，CEF通过上调GLT-1的表达和谷氨酸摄取来保护神经元免受全脑缺血的影响。
Ceftriaxone(Cef) selectively increases the expression of glial glutamate transporter-1 (GLT-1), which was thought to be neuroprotective in some circumstances. However, the effect of Cef on glutamate uptake of GLT-1 was mostly assayed using in vitro studies such as primary neuron/astrocyte cultures or brain slices. In addition, the effect of Cef on neurons in different ischemic models was still discrepant. Therefore, this study was undertaken to observe the effect of Cef on neurons in global brain ischemia in rats, and especially to provide direct evidence of the up-regulation of GLT-1 uptake for glutamate contributing to the neuronal protection of Cef against brain ischemia. Neuropathological evaluation indicated that administration of Cef, especially pre-treatment protocols, significantly prevented delayed neuronal death in hippocampal CA1 subregion normally induced by global brain ischemia. Simultaneously, pre-administration of Cef significantly up-regulated the expression of GLT-1. Particularly, GLT-1 uptake assay with 3H-glutamate in living cells from adult rats showed that upregulation in glutamate uptake accompanied up-regulated GLT-1 expression. Inhibition of GLT-1 by antisense oligode-oxynucleotides or dihydrokainate significantly inhibited the Cef-induced up-regulation in GLT-1 uptake and the neuroprotective effect against global ischemia. Thus, we may conclude that Cef protects neurons against global brain ischemia via upregulation of the expression and glutamate uptake of GLT-1.