| Constant decrease of cerebral blood flow in chronic cerebral ischemia easily lead to the acquired and progressive cognitive dysfunction and its main clinical manifestations is the decline in learning and memory. Normally, dysfunction resulting from cerebral ischemia is closely related to the difficulty of regeneration after damage of central nervous system(CNS)[1]. Regeneration dysfunction of CNS has many complicated reasons. Recent researches mainly focus on myelin-associated inhibitors, i.e. Nogo-A, OMgp and MAG[2], impeding the nerve regeneration and functional recovery of nerve system. Among them, related research has shown the correlation between Nogo-A and cognitive function dysfunction resulted from chronic cerebral ischemia. However, there is no report about the relationship between OMgp(or MAG) and cognitive function dysfunction. Moreover, many studies exhibit that vinpocetine can improve cognition[3]. Basic research of Vinpocetine has been reported few on the role of cognitive decline induced by chronic ischemia, without experimental study related with MAIs.We aimed to establish the chronic cerebral ischemia model in the rat with the permanen bilateral carotid artery occlusion. To observe the expression change of Nogo-A, OMgp and MAG, the myelin-associated inhibitory factors of axonal regeneration in the chronic cerebral ischemia of rats' hippocampus region and the impact of Vinpocetine of all. To explore mechanism of cognitive dysfunction after chronic cerebral ischemia and provide the neuron protective mechanism of Vinpocetine.The healthy male Wistar rats were randomly divided into sham-operated group, model group, high-dose Vinpocetine group, low-dose Vinpocetine group. Each group according to ischemic time was subdivided into 3, 6 and 9 weeks groups. eventually assign each group of 6 rats. This experiment uses a bilateral common carotid artery permanent occlusion(2VO) to prepare a chronic cerebral ischemia rat model. The rats' cognitive function of each groups were tested by Morris water maze on different time(3, 6, 9weeks) after 2VO. The change of pathology in each group rats' hippocampus region was determined by HE staining. Use Immunohistochemistry to detect the expression of protein of Nogo-A, OMgp and MAG and situ hibridization to detect the expression of Nogo-A mRNA in each group rats' hippocampus region.Compared with shamed group, the escape latency was extended(P<0.01), the number that rats passed through the platform was reduced(P<0.05). they change gradually with time. Compared with shamed group, HE dispays the neuron in hippocampus of model rats degeneration and necrosis, the number of losing, and gradually increased with time. the expression of Nogo-A, OMgp and MAG protein and Nogo-A mRNA in hippocampal areas of model group significantly increased(P<0.01) than the shamed group. In the Vinpocetine High and low dose groups, the escape latency is significately shorter(P<0.05) and the across paltform number increased(P<0.05) compared with the model group. The pathological changes in hippocampal areas at three time points compared with the model group of the same point in time have lessened in different degrees. The expression of Nogo-A, OMgp, MAG protein and Nogo-A mRNA in hippocampal areas of Vinpocetine High and Low dose groups were reduced compared with the model group(P<0.05).The cognitive dysfunction of the rats caused by chronic cerebral ischemia has a progression in time course. The high expression of Nogo-A, OMgp and MAG, the myelin-associated inhibitory factors, is participate in the suppression of Nerve regeneration during chronic cerebral ischemia. Vinpocetine can improve the cognitive dysfunction in chronic cerebral ischemia rats, and vinpocetine may play a neuroprotective effect on Nerve regeneration by inhibiting Nogo-A, OMgp and MAG. |
PDF Full Text Request