Neuronal Protective Effect About Angelica Compensating Cognitive Deficits In Chronic Cerebral Ischemia Rat

Induction : Cerebral ischemia are the main cause of Vascular Cognitive Impairment (VCI) often leading to exaggerated brain damage and cognitive impairment. That endogenous NGF and BDNF can increase the activity of cholinergic system of the basal forebrain and the plasticity of neuron of hippocampus is thought to contribute to the improvement of cognitive function impairment. Chinese Angelica showed beneficial effects on the performance of learning impairment. But VCI induced by chronic cerebrovascular ischemia (chronic cerebral hypoperfusion) is expected to be clarified.Objective:1. In this paper, we observed the level of mRNA and protein of NGF and BDNF from hippocampus of chronic cerebral hypoperfusion in rats.2. We Attempted to visualize whether angelica can improve the cognitive function impairment of rat induced by chronic cerebral hypoperfusion.3. And we tried to investigate whether it is mediated by inducing the level of endogenous NGF or BDNF in hippocampus of rat that angelica could compensate the cognitive deficits and cerebrovascular breakdown induced by experimental chronic cerebral hypoperfusion.Method:1. The rats were divided into three groups: angelica treatment group, saline administration group and sham operation group.2. Permanent occlusion of bilateral common carotid occlusion (2VO) was used to induce a chronic reduction of cerebral blood flow to the brain of rat. Angelica treatment group were treated with angelica (25% angelica injection) at a dose of 20ml/kg given by intraperitoneal injection once daily for two months after 2VO surgery completed. Saline administration group were given saline solution 0.9% during the same time. Sham operation group were given no treatment.3. Two months after 2VO, spatial learning and memory performance were examined in rat using a Morris water maze task.4. The sections of rat brain were processed by immunohistochemistry S-P with antibody against BDNF and NGF. The pathological immunoreactivity in hippocampus was observed under light microscope.5. The mRNA level of NGF and BDNF from three groups was measured using SYBR Green real-time RT-PCR.6. And the protein level of NGF and BDNF were measured using Western blotting.Result:1. Two months after 2VO surgery, the sham operation exhibited longer escape latencies throughout the training days than the angelica treatment group, but shorter than the saline administrated group.2. Both of NGF and BDNF mRNA expression in hippocampus of the saline administrated group were up-regulated, compared to that of the sham operation, but decreasing compared to the angelica treatment group.3. A significant elevation hippocampal BDNF protein and a light elevation hippocampal NGF protein in the angelica treatment group were found, compared to the saline administrated group.4. But defferential expression of hippocampal NGF protein and mRNA were not significant among the three groups.Conclusion: angelica can improve the spatial memory impairment induced by chronic cerebral hypoperfusion. Probably it is mediated by inducing the lever of endogenous BDNF in hippocampus of rat that angelica could protect the cognitive deficits induced by chronic cerebral hypoperfusion.