Expression of Voltage-Gated Sodium Channel Nav1.3 Is Associated with Severity of Traumatic Brain Injury in Adult Rats
Expression of Voltage-Gated Sodium Channel Nav1.3 Is Associated with Severity of Traumatic Brain Injury in Adult Rats
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电压门控钠通道 Nav1.3 的表达与成年大鼠创伤性脑损伤的严重程度相关
DOI：
10.1089/neu.2012.2508
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发表时间：
2013-01-01
影响因子：
4.2
通讯作者：
Jiang, Ji-yao
中科院分区：
文献类型：
--
作者：
Huang, Xian-jian;Mao, Qing;Jiang, Ji-yao
在创伤性脑损伤（TBI）后的继发性损伤期，由电压门控钠通道（VGSC）介导的神经元去极化导致细胞异常和神经功能障碍。VGSC的不同α亚基表达的改变可以影响TBI后的早期脑病理学。本研究检测了TBI后大鼠大脑皮质Nav1.3 mRNA和蛋白的表达。成年雄性Sprague-Dawley大鼠随机分为假TBI、轻度TBI（mTBI）或重度TBI（sTBI）组。使用液压冲击装置在1.5-1.6 atm（mTBI）和2.9-3.0 atm（sTBI）的幅度下诱导TBI。采用实时定量逆转录聚合酶链反应（RT-PCR）和免疫印迹法（Western blot）检测脑损伤后2 h、12 h、24 h和72 h同侧皮质Nav1.3 mRNA和蛋白水平。在TBI后24小时、72小时和7天收集脑用于TUNEL染色和细胞计数分析。免疫荧光检测损伤侧皮质Nav1.3蛋白的表达。与假TBI组相比，mTBI组和sTBI组在TBI后2 h和12 h的Nav1.3 mRNA和蛋白表达均显著上调。sTBI组Nav1.3 mRNA和蛋白表达水平在伤后12 h明显高于mTBI组。在TBI后24小时、72小时和7天，sTBI组的TUNEL阳性细胞数显著高于mTBI组。Nav1.3主要在皮层神经元中表达。这些结果表明，在大鼠TBI后的极早期阶段，同侧损伤皮层中Nav1.3 mRNA和蛋白的表达显著上调，并且还与TBI严重程度相关。
During the secondary injury period after traumatic brain injury (TBI), depolarization of neurons mediated by voltage-gated sodium channels (VGSCs) leads to cellular abnormalities and neurological dysfunction. Alterations in expression of different alpha subunits of VGSCs can affect early brain pathology following TBI. This study detected the expression of Nav1.3 mRNA and protein in the rat cortex post-TBI. Adult male Sprague-Dawley rats were randomly assigned to sham-TBI, mild-TBI (mTBI), or severe-TBI (sTBI) groups. TBI was induced using a fluid percussion device at magnitudes of 1.5-1.6 atm (mTBI) and 2.9-3.0 atm (sTBI). Nav1.3 mRNA and protein levels in the ipsilateral-injured cortex were examined at 2 h, 12 h, 24 h, and 72 h post-TBI by real-time reverse transcriptase quantitative polymerase chain reaction and Western blot. Brains were collected at 24 h, 72 h, and 7 days post-TBI for TUNEL staining and cell count analysis. Immunofluorescence was performed to localize expression of Nav1.3 protein in the ipsilateral-injured cortex. Expression of Nav1.3 mRNA and protein were significantly upregulated in mTBI and sTBI groups when compared with the sham-TBI group at 2 h and 12 h post-TBI. Nav1.3 mRNA and protein levels in the sTBI group were much higher than in the mTBI group at 12 h post-TBI. TUNEL-positive cell numbers were significantly higher in the sTBI group than in the mTBI at 24 h, 72 h, and 7 days post-TBI. Expression of Nav1.3 was observed predominantly in neurons of the cortex. These findings indicated significant upregulation in the expression of Nav1.3 mRNA and protein in the rat ipsilateral-injured cortex at the very early stage post-TBI, and were also correlated with TBI severity.