Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats
Activation of mGluR5 Attenuates Microglial Activation and Neuronal Apoptosis in Early Brain Injury After Experimental Subarachnoid Hemorrhage in Rats
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mGluR5 的激活减弱大鼠实验性蛛网膜下腔出血后早期脑损伤中的小胶质细胞激活和神经元凋亡
DOI：
10.1007/s11064-015-1572-7
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发表时间：
2015-06-01
影响因子：
4.4
通讯作者：
Huang, Si-luo
中科院分区：
文献类型：
--
作者：
Zhang, Zong-yong;Sun, Bao-liang;Huang, Si-luo
代谢型谷氨酸受体 5 (mGluR5) 的激活在多发性中枢神经系统损伤中提供神经保护作用，但 mGluR5 在蛛网膜下腔出血 (SAH) 中的作用仍不清楚。在本研究中，我们旨在评估 mGluR5 的激活是否可以减轻大鼠实验性蛛网膜下腔出血后的早期脑损伤 (EBI)。我们发现，SAH 后 24 小时，选择性 mGluR5 正构激动剂 CHPG 或正变构调节剂 VU0360172 给药可显着改善神经功能并减轻脑水肿。此外，mGluR5在SAH后活化的小胶质细胞（ED-1阳性）中明显表达。 SAH 后 24 小时，CHPG 或 VU0360172 给药可显着降低活化小胶质细胞的数量以及促炎细胞因子 IL-1β、IL-6 和 TNF-α 的蛋白质和 mRNA 水平。此外，CHPG 或 VU0360172 给药明显减少 SAH 后 24 小时皮质中 TUNEL 阳性细胞和活性 caspase-3/NeuN 阳性神经元的数量。 CHPG或VU0360172给药显着上调Bcl-2的表达，下调Bax和活性caspase-3的表达，从而增加Bcl-2/Bax的比率。我们的结果表明，mGluR5 的激活减弱了小胶质细胞的激活和神经元凋亡，并改善了 SAH 后 EBI 的神经功能。
Activation of metabotropic glutamate receptor 5 (mGluR5) provided neuroprotection in multiple central nervous system injury, but the roles of mGluR5 in subarachnoid hemorrhage (SAH) remain unclear. In present study, we aimed to evaluate whether activation of mGluR5 attenuates early brain injury (EBI) after experimental SAH in rats. We found that selective mGluR5 orthosteric agonist CHPG or positive allosteric modulator VU0360172 administration significantly improves neurological function and attenuates brain edema at 24 h after SAH. Furthermore, mGluR5 obviously expresses in activated microglia (ED-1 positive) after SAH. CHPG or VU0360172 administration significantly reduces the numbers of activated microglia and the protein and mRNA levels of pro-inflammatory cytokines IL-1β, IL-6 and TNF-α at 24 h after SAH. Moreover, CHPG or VU0360172 administration obviously reduces the number of TUNEL-positive cells and active caspase-3/NeuN-positive neurons in cortex at 24 h after SAH. CHPG or VU0360172 administration significantly up-regulates the expression of Bcl-2, and down-regulates the expression of Bax and active caspase-3, which in turn increases the ratio of Bcl-2/Bax. Our results indicate that activation of mGluR5 attenuates microglial activation and neuronal apoptosis, and improves neurological function in EBI after SAH.