The Vagus Nerve Stimulation In Cerebral Ischemia Protection Effects On Related Immune Regulation

Objective: Vagus nerve Stimulation(VNS) treatment of epilepsy has been a long-termdevelopment and achieved good effect. With the numerous increase in the studies ofVNS therapy of cerebral ischemia in recent years, protection mechanism of VNSagainst cerebral ischemia emerged gradually and differed. This study aimed todetermine the effect of long-run and short-run stimulus on infarct volume of rats. Toinvestigate the expression of TNF-α and IL-6in focal cerebral ischemia rats, and toexplore VNS in cerebral ischemia protection effects on related immune regulation.Methods:108adult male rats were distributed into sham group(36rats), controlgroup(36rats) and VNS-treated group(36rats). Each group was divided into6subgroups (12h,1d,2d,3d,7d,14d subgroup). Transient ischemia was produced byfilament occlusion of the right MCA for120min followed by reperfusion. The rightvagus nerve was stimulated at required time after the induction of ischemia anddelivered for30seconds every5minutes for a total period of60minutes. Square Pulseswere delivered and constant current unit at0.5mA,30s train of0.5ms pulses deliveredat20Hz. Neurological evaluations were performed in all animals at12h,1d,2d,3d,7dand14d after MCA occlusion and animals were euthanized to determine the ischemialesion volume at each subgroup. Expressions of tumor necrosis factor-α(TNF-α) andinterleukin-6(IL-6) in rat brain were determined by ELISA and Western blot．Results:1. Control animals had better scores at12h,1d,2d,3d,7d and14d comparedwith the sham animals and infarct sizes was larger in control animals than that in shamanimals (p<0.05);2. Ischemic lesion volumes in VNS-treated group were smaller thancontrol animals (p<0.05);3. Although the functional score in both treated and untreatedgroups improved over the observation period (p<0.01), and in addition there was still astatistically significant improvement due to VNS treatment compared with controlanimals (p<0.05);4. Compared with the sham animals, the expressions of TNF-α and IL-6in control animals were significantly higher than that in the sham animals at eachsubgroup respectively(P<0.05), and rose to the highest point at24h，then graduallyreduced，dropped to normal level at7d and14d;5. The content of TNF-α and IL-6inVNS-treated group were lower than control group(p<0.05).Conclusion: Both the long and short-term stimulus have comparable effects. Theneuroprotective effect of VNS on cerebral ischemia may be bound up with inhibitedexpressions of TNF-α and IL-6.