Vevom Nerve Growth Factor Promote Neural Plasticity Of A Rat Ischemia/Repufusion Model: An Experimental Study

Objective:To investigate the effect of intracerebroventricular administra tion of vevom nerve growth factor on proliferation and migration of endogenous neural progenitor cells in rats with cerebral ischemia/reperfusion injury.Methods:Wistar rats were randomly divided into three groups:2 days group, 7 days group and 14 days group (n= 30 in each group), then each group randomly assigned to vNGF 25u, vNGF 50u, vNGF 1OOu, sham-operation, and ischemia/reperfusion control subgroups (n=6 in each subgroup). After that a focal cerebral ischemia/reperfusion model was induced by middle cerebral artery intraluminal suture occlusion (MCAO) method in the I/R control and vNGF subgroups. Normal saline or Different concentrations vNGF was administered via intracerebroventricular to the I/R control or vNGF subgroups rats per day according to the corresponding time points. After cerebral ischemia /reperfusion injury was established, the degree of neurological functional recovery of rats was assessed by longa score, and the numbers of positive cells of DCX+ cells and ERK+ cells in the Peri-ischemic cortex and Hippocampus CA3/DG were assessed by immunohistochemical method in the corresponding time points.Result:1, As compared with control subgroups, snake venom nerve growth factor subgroups which was administered via intracerebroventricular, the neurological function began to recover in the first two days. Each subgroups by statistical analysis, the statistically difference was significant (P<0.05), which showed its positive intervention effects markedly. However, there were no ischemia/reperfusion injury in Sham-operated subgroups.The results of DCX immuno-histochemistry showed that:the numbers of DCX positive cells in Peri-ischemic cortex and Hippocampus CA3/DG of snake venom nerve growth factor subgroups began to increase at 2 days after the procedures, reach the peak at 7 days, the first decline in 14 days. As compared with the I/R control subgroups, the trend was markedly higher. The vNGF50u subgroups expressed much more DCX+ cells than other subgoups at the corresponding time points, which showed its positive intervention of dose-response effects markedly; Among them, the numbers of DCX positive cells vNGF 50u subgroup in the 7th day were significantly higher than those vNGF 50u subgroups in 2 day or 14 day, which showed its positive intervention of aging-response effects markedly. The differences aresignificant (P<0.03).3,The results of ERK immunohisto-chemistry showed that:the numbers of ERK positive cells in Peri-ischemic cortex and Hippocampus CA3/DG of snake venom nerve growth factor subgroups reach the peak at 2 days after the procedures, began to decline at 7 days, then restored baseline levels at 14 days. As compared with the I/R control subgroups, snake venom nerve growth factor subgroups showed a clear down-ward trend. The vNGF50u subgroups expressed much less ERK positive cells than other subgoups at the corresponding time points, Especially at the 7days, which showed its negative intervention of dose-response effects markedly.Conclusions:1, The cerebral ischemia/repufusion injury can induce proliferation and migration of endogenous neural progenitor cells in the Peri-ischemic cortex and Hippocampus CA3/DG.2, Exogenous snake venom nerve growth factor can effectively compensate for the insufficient of endogenous nerve growth factor after cerebral ischemia/repufusion injury, as well as facilitate proliferation and migration of endogenous neural progenitor cells in the Peri-ischemic cortex and Hippocampus CA3/DG.3,The significant differences expression levels of ERK-positive cells among the three groups, suggesting that NGF may play a negative regulator in ERK, which provide a possible theoretical source for NGF on vascular regeneration and the role of neurogenesis.4,The significant differences expression of ERK and DCX-positive cells in the Peri-ischemic cortex and Hippocampus CA3/DG suggesting that there maybe had an association between ERK and the prolife-ration and migration of the DCX after reperfusion.