The up-regulation of voltage-gated sodium channel Nav1.6 expression following fluid percussion traumatic brain injury in rats.
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 alpha-subunit has occurred in a variety of neuropathological states including focal cerebral ischemia, spinal injury, and epilepsy.


OBJECTIVE
In this study, changes in Nav1.6 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.


CONCLUSIONS
Results of the study showed significant up-regulation of mRNA and protein for Nav1.6 in rat hippocampal neurons after TBI.
Mao
Qing
Q
Department of Neurosurgery, Shanghai RenJi hospital, Shanghai Jiaotong University, School of Medicine, People's Republic of China.
Jia
Feng
F
Zhang
Xiao-Hua
XH
Qiu
Yong-Ming
YM
Ge
Jian-Wei
JW
Bao
Wen-Jing
WJ
Luo
Qi-Zhong
QZ
Jiang
Ji-Yao
JY
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D018390:Gene Targeting / Q000379:methods*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008297:Male; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics*
D062557:NAV1.6 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C507811:Scn8a protein, rat; D015222:Sodium Channels