Differential hippocampal protection when blocking intracellular sodium and calcium entry during traumatic brain injury in rats.
Differential hippocampal protection when blocking intracellular sodium and calcium entry during traumatic brain injury in rats.
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大鼠创伤性脑损伤期间阻断细胞内钠和钙进入时的差异性海马保护。
DOI：
10.1089/neu.2008.0635
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发表时间：
2008
影响因子：
4.2
通讯作者：
Lyeth,BruceG
中科院分区：
文献类型：
--
作者：
Zhao,Xueren;Gorin,FredricA;Berman,RobertF;Lyeth,BruceG
本研究探讨了钠-钙交换蛋白(NCX)和钠-质子逆向转运蛋白(NHE-1)的逆转模式在大鼠液压脑损伤(TBI)后海马区急性星形胶质细胞和神经元病理变化中的作用。分别抑制NCX、NHE-1或NCX、NHE-1和ASIC1a(1a型酸敏离子通道)的KB-R7943、EIPA或阿米洛利在脑损伤前60分钟脑室注入。伤后24 h，星形胶质细胞进行胶质纤维酸性蛋白免疫组织化学染色，荧光JADE染色鉴定变性神经元。对海马区CA2/3亚区的体视学分析表明，与赋形剂处理的动物相比，较高剂量的KB-R7943(2和20摩尔)显著降低了星形胶质细胞GFAP的免疫反应。EIPA(2-200nmols)对星形胶质细胞GFAP免疫反应无明显影响。阿米洛利(100nmoles)可显著减轻脑损伤引起的星形胶质细胞GFAP免疫反应的急性降低。在被检查的三种化合物中，只有阿米洛利(100nmoles)减少了用氟-翡翠评估的海马神经元变性。这些结果为脑外伤后海马区的急性星形胶质细胞病理提供了进一步的证据，同时表明NHE-1的激活和NCX的逆转模式在实验性脑损伤后的星形胶质细胞和神经元病理中都起到了作用。
This study investigated the contributions of the reverse mode of the sodium-calcium exchanger (NCX) and the type 1 sodium-proton antiporter (NHE-1) to acute astrocyte and neuronal pathology in the hippocampus following fluid percussion traumatic brain injury (TBI) in the rat. KB-R7943, EIPA, or amiloride, which respectively inhibit NCX, NHE-1, or NCX, NHE-1, and ASIC1a (acid-sensing ion channel type 1a), was infused intraventricularly over a 60-min period immediately prior to TBI. Astrocytes were immunostained for glial fibrillary acidic protein (GFAP), and degenerating neurons were identified by Fluoro-Jade staining at 24 h after injury. Stereological analysis of the CA2/3 sub-regions of the hippocampus demonstrated that higher doses of KB-R7943 (2 and 20 nmoles) significantly reduced astrocyte GFAP immunoreactivity compared to vehicle-treated animals. EIPA (2–200 nmoles) did not alter astrocyte GFAP immunoreactivity. Amiloride (100 nmoles) significantly attenuated the TBI-induced acute reduction in astrocyte GFAP immunoreactivity. Of the three compounds examined, only amiloride (100 nmoles) reduced hippocampal neuronal degeneration assessed with Fluoro-Jade. The results provide additional evidence of acute astrocyte pathology in the hippocampus following TBI, while suggesting that activation of NHE-1 and the reverse mode of NCX contribute to both astrocyte and neuronal pathology following experimental TBI.