title: Expression of voltage-gated sodium channel Nav1.3 is associated with severity of traumatic brain injury in adult rats.
abstract: 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 α 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.
authors.affiliation: Department of Neurosurgery, Shanghai Renji Hospital, Shanghai Jiaotong University , School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xian-jian
authors.initials: XJ
authors.lastname: Huang
authors.forename: Qing
authors.initials: Q
authors.lastname: Mao
authors.forename: Yong
authors.initials: Y
authors.lastname: Lin
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Ji-yao
authors.initials: JY
authors.lastname: Jiang
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015601:Injury Severity Score; D008297:Male; D062552:NAV1.3 Voltage-Gated Sodium Channel / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000235:genetics*
chemical_list: D062552:NAV1.3 Voltage-Gated Sodium Channel; D012333:RNA, Messenger