Orexin-A Is Involved In The Upregulation Of NMDA Receptor Subunit NR1 Caused By Vugal Nerve Stimulation In Traumatic Brain Injury-induced Coma

Objective: To investigate the wake-promoting action of vagus nerve stimulation and its influences on the expression of N-methyl-D-aspartate Receptor subunit NR1 in the prefrontal cortex of rats with TBI-indued coma,and to further clarify whether Orexin-A mediated this effect of VNS.Method: One hundred and forty-four sprague-dawley rats were divided into four groups: control,model(TBI),stimulated(TBI+VNS)and Orexin-1 receptor antagonist group(TBI+SB334867+VNS).Rats post-TBI were performed with a vagus nerve stimulator device,the behavior of the rats were observed.The prefrontal cortex tissues of each rat was separated and extracted at 6,12,24 hour after VNS,and the expression of NR1 in this area was evaluated by using immunohistochemistry and western blot assays.Result: Twenty-three rats re-awaked in simulated group,while there were only eleven and sixteen rats exhibited righting reflex in model and antagonist group,respectively.Comparisons between two groups showed that the expression of NR1 in sham stimulated group was significantly lower than that in control group(P < 0.05),and NR1 expression in stimulated group was significantly higher than that in sham stimulated group(P < 0.05),while NR1 showed an statistically increasing trend in antagonist group when compared with stimulated group(P < 0.05).Comparison of the NR1 expression within groups revealed the following trend: 24 hours <12hours<6hours in the stimulated group(P<0.05),and 6 hours<12hours<24hours in the TBI groups(P<0.05).Conclusion: Vagus nerve stimulation contributes to the recovery of consciousness from TBI-indued coma,and this effect may be due to an upregualtion of NR1 in the prefrontal cortex via activating orexin-A in brain.