Effect Of Vagus Nerve Stimulation On Consciousness And Expression Of ?-aminobutyric Acid B Receptor In Coma Rats Following Traumatic Brain Injury

Objective:To investigate the wake-promoting effect of vagus nerve stimulation(VNS),investigate changes of GABAb1 receptor(GABAb1R)expression in prefrontal cortex(PFC)and the relationship with Orexin system in traumatic brain injury(TBI)induced comatose rats following VNS.Methods:Sprague Dawley rats were randomly divided into 4 groups(n=42): control group,TBI group,VNS group and Orexin 1 receptor(OX1R)antagonist group.We applied VNS to rats which were in coma state which experience “Free-fall drop” that caused coma and we classified consciousness level according rat's behaviours,then rats were sacrified and PFC was extracted at 6 h,12 h,24 h time points after the experiment.Western-blotting and immunohistochemistry techniques were used to detect the expressions of GABAb1 R in PFC.Results:Rats following "free-fall drop " showed behavioral changes similar to clinical coma,while after VNS,the comatose rats showed transient behavioral arousal.The rats in blank control group all awakened,11 rats in TBI group,28 rats in VNS group,13 rats in OrexinA antagonist group awakened,consciousness level showed an "Blank > VNS > antagonist > TBI" trend among four groups of rats,differences between groups had statistical significance(P < 0.05).Western Blot results show that,at different time points,GABAb1 R expression in TBI group,VNS group,antagonist group in the PFC showed a "6 h > 12 h > 24 h" trend,this difference in VNS group was statistically significant(P < 0.05),GABAb1 R expression in PFC of blank group showed "12 h > 24 h > 6 h" trend,there was no statistically significant difference(P >0.05).At 6 h timepoint,GABAb1 R expression showed an " Blank < VNS <antagonism < TBI " increasing trend among four groups,the difference wasstatistically significant(P< 0.05)comparing any two groups,at 12 h,24 h time points,GABAb1 R expression showed a " VNS < Blank < antagonism < TBI " increasing trend,the difference was statistically significant(P < 0.05)comparing any two groups.Immunohistochemical results showed that GABAb1 R expression had "Blank < VNS< antagonism < TBI " increasing trend,the difference was statistically significant(P <0.05),GABAb1 R expression in prefrontal cortex at three time points showed " 6 h >12 h > 24 h " trend,the differences had no statistical significance(P > 0.05).Conclusion:VNS has wake-promoting effect,the mechanism may be related to downregulation of GABAb1 R expression induced by OrexinA in PFC,and OrexinA may act as a swith in promoting the wakefulness of coma by TBI.