The Up-Regulation of Voltage-Gated Sodium Channel NaV1.6 Expression Following Fluid Percussion Traumatic Brain Injury in Rats
The Up-Regulation of Voltage-Gated Sodium Channel NaV1.6 Expression Following Fluid Percussion Traumatic Brain Injury in Rats
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DOI：
10.1227/01.neu.0000369612.31946.a2
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发表时间：
2010-06-01
期刊：
影响因子：
4.8
通讯作者：
Jiang, Ji-yao
中科院分区：
文献类型：
--
作者：
Mao, Qing;Jia, Feng;Jiang, Ji-yao
背景：由电压门控钠通道(VGSCs)介导的Na+内流和去极化是创伤性脑损伤所致细胞异常的早期事件，因此被认为是药物调控脑损伤病理反应的上游靶点。在大鼠局灶性脑缺血、脊髓损伤和癫痫等多种神经病理状态下，VGSCα亚单位的表达都发生了变化。目的：本研究观察了大鼠脑损伤后海马区Na(V)1.6mRNA和蛋白表达的变化。用侧向液压冲击装置诱发颅脑损伤。用实时定量聚合酶链式反应和Western印迹法检测损伤后2、12、24、72h双侧海马区Nav1.6基因的表达。结果：脑挫伤后2小时和12小时，大鼠双侧海马区Nav1.6蛋白表达明显上调。在脑损伤后2-72小时，同侧海马区Nav1.6蛋白表达显著上调，而在脑损伤后2-24小时，对侧海马区Nav1.6蛋白表达显著上调。结论：颅脑损伤后大鼠海马神经元中Nav1.6的表达明显上调。
BACKGROUND: The influx of Na+ and the depolarization mediated by voltage-gated sodium channels (VGSCs) is an early event in traumatic brain injury (TBI) induced cellular abnormalities and is therefore well positioned as an upstream target for pharmacologic modulation of the pathological responses to TBI. Alteration in the expression of the VGSC a-subunit has occurred in a variety of neuropathological states including focal cerebral ischemia, spinal injury, and epilepsy.OBJECTIVE: In this study, changes in Na(v)1.6 mRNA and protein expression were investigated in rat hippocampus after TBI.METHODS: Forty-eight adult male Sprague Dawley rats were randomly assigned to control or TBI groups. TBI was induced with a lateral fluid percussion device. Expression of mRNA and protein for Nav1.6 in the bilateral hippocampus was examined at 2, 12, 24, and 72 hours after injury by real-time quantitative polymerase chain reaction and Western blot. Immunofluorescence was performed to localize the expression of Nav1.6 protein in the hippocampus.RESULTS: Expression of Nav1.6 mRNA was significantly up-regulated in the bilateral hippocampus at 2 and 12 hours post-TBI. Significant up-regulation of Nav1.6 protein was identified in the ipsilateral hippocampus from 2 to 72 hours post-TBI and in the contralateral hippocampus from 2 to 24 hours post-TBI. Expression of Nav1.6 occurred predominantly in neurons in the hippocampus.CONCLUSION: Results of the study showed significant up-regulation of mRNA and protein for Nav1.6 in rat hippocampal neurons after TBI.