The Up‐Regulation of Voltage‐Gated Sodium Channel NaV1.6 Expression Following Fluid Percussion Traumatic Brain Injury in Rats

BACKGROUNDThe 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 α-subunit has occurred in a variety of neuropathological states including focal cerebral ischemia, spinal injury, and epilepsy. OBJECTIVEIn this study, changes in Nav1.6 mRNA and protein expression were investigated in rat hippocampus after TBI. METHODSForty-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. RESULTSExpression 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. CONCLUSIONResults of the study showed significant up-regulation of mRNA and protein for Nav1.6 in rat hippocampal neurons after TBI.