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 voltagegated sodium channels (VGSCs) leads to cellular abnormalities and neurological dysfunction. Alterations in expression of different a 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.

Deep sequencing and miRNA profiles in alcohol-induced neuroinflammation and the TLR4 response in mice cerebral cortex

“…Early studies also have demonstrated that a high anesthetic alcohol concentration inhibits sodium channel Nav1.3 91 , although lower alcohol levels, which occurs in chronic alcohol treatment, can promote adaptation by increasing its expression levels since the up-regulation of Nav1.3 is associated with traumatic brain injury severity in rats 92 . The other gene is vanilloid receptor TRPV1, a multimodal ion channel of afferent neurons that seems to play a role in hyperalgesia associated with inflammation 93 , 94 .…”

Knockout of Cyclophilin-D Provides Partial Amelioration of Intrinsic and Synaptic Properties Altered by Mild Traumatic Brain Injury

“…The changes in AP and AHP amplitude are likely due to altered sodium and potassium channel densities and/or current amplitudes. Other models of TBI have been shown to alter current amplitude and expression of sodium and potassium channels (D’Ambrosio et al, 1999 ; Hains et al, 2005 ; Lampert et al, 2006 ; Mao et al, 2010 ; Lei et al, 2012 ; Huang et al, 2013 ; Takahashi et al, 2013 ). The CypDKO reversed much of the increased membrane excitability induced by mTBI, including the AP and AHP amplitudes.…”

MRI Evidence of Altered Callosal Sodium in Mild Traumatic Brain Injury

“…The findings corroborate a growing body of literature that underscores the importance of cytosolic sodium as a marker of tissue injury after trauma. In mTBI, twisting and stretching of axons results in mechanical disruption of membranes, altered function of voltage-gated sodium channels and sodium-potassium adenosine triphosphatase, 4,5,22 and changed regulation of the expression of sodium channels, 6,7 with potential persistent sodium abnormality.…”