| Objective:After adult mammalian central nervous system injuried, their action recovery is limited.This limit is mainly due to the lack of axonal regeneration.So,the research of plasticity of nerve regeneration pathways is the core problem to research paralysis and rehabilitation mechanism after the injury of cerebral ischemic-reperfusion.In spinal cord damage model,intrathecal injection of NEP1-40 can cause corticospinal tract(CST) patency gemmation and action improvement.It was not know that NEP1-40 whether or not have also utility in middle cerebral artery ischemicreperfusion (MCAI/R)model.In this study,the changes of growth associated protein(GAP-43)and RhoA expression was determined by western blot(WB) technique,the left forelimb motor function was test by the "staircase test" designed by Montoya in rat MCAI/R model.To study the effects of NEP1-40 on axon regeneration,motor function recovery of affected limb and RhoA signal pathway in cerebral ischemia-reperfusion rats,for exploring its possible mechanism.Methods:(1)Choose left-handed adult male SD rats after "staircase test" training,and separated them into the sham operation group(sham group),the ischemia control group(control group),the intra-lateral ventricle injection of PBS group(PBS group) and the intra-lateral ventricle injection of NEP1-40 group(NEP1-40 group),then test the left forelimb function on the day before MCAI/R model established,the 7d,14d and 21d after MCAI/R model established.(2)The sham group just get the external carotid artery liqation,and the remaining groups get the establishing MCAI/R model.(3)The PBS group and NEP1-40 group discern to finish intra-lateral ventricle injection at the 24h after established MCAI/R model.(4)The changes of GAP-43 and RhoA expression were determined by western blot technique at 7d,14d and 21d after MCAI/R model established.Results:(1)The expression of GAP-43 in control group increased to the maximum at 7d after MCAI/R,decreased at 14d(P＜0.05),but still higher than sham group,then to decreased to sham group's level at 21d(P＞0.05).(2)The expression of GAP-43 in NEP1-40 group were higher than that in control and PBS group at 7d and 14d after MCAI/R(P＜0.05),especially at 7d.(3)The expression of RhoA in control group increased to the maximum at 7d after MCAI/R,then decreased but still much higher than that in sham group at 14d and 21d(P＜0.05).(4)The expression of RhoA in NEP1-40 group were much lower than that in control and PBS group at every time point(P＜0.05).(5)The compare of snatch ability of left forelimb had no statistic difference on the 1d before MCAI/R model established(P＞0.05).The results of"staircase test " in control,PBS and NEP1-40 group at each time point had the same change tendency,the results of "staircase test" in NEP1-40 group were much higher than that in control group and PBS group at each time point after MCAI/R(P＜0.05).Conclusion:(1)The expression of GAP-43 and RhoA are synchronism up-regulation in the acute phase and recovery phase of cerebral ischemia injury.(2)Intra-lateral ventricle injection of NEP1-40 can increase the expression of GAP-43 and inhibit the expression of RhoA.(3)intra-lateral ventricle injection of NEP1-40 can improve axon regeneration and promote the recovery of motor function after central nervous system injury.(4)All the research conclusion show that the NEP1-40 can improve axon regeneration in cerebral ischemia-reperfusion rats and promote motor function recovery of affected limb through promoting the expression of GAP-43 and inhibiting the expression of RhoA,which show it is potential to treat the ischemia.NEP1-40 promote axon regeneration and the recovery of motor function,that it might be through regulating RhoA signal pathway.
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