Protective Effects Of Breviscapine On Ischemic Vascular Dementia In Rats

PartⅠEffects of breviscapine on learning and memory in vascular dementia ratsObjective: To investigate the action and mechanism of breviscapine on the ability of learning and memory of vascular dementia rats.Methods: The permanent occlusion of bilateral common carotid arteries model was used to mimic VD. The effect of breviscapine was observed by Morris water maze test, histopathological observation, biochemical analysis of SOD and MDA.Results: (1) In Morris water maze test, the escape latency in sham-operated group and treated-group were 13.87±6.31 s and 15.12±8.25 s, respectively. The VD rats in model group spent 44.25±11.04 s in finding the platform. Compared with the model group, the escape latency in sham-operated group and treated-group was significantly shortened (P<0.05).(2) In the histopathological observation, the permanent occlusion of bilateral common carotid arteries caused histological appearance of neuron injury in hippocampal CA1 area of model group. Pyramidal cellular nuclear was shrinked and accompanied by cellular edema. Furthermore, the pyramidal layer was disordered and irregular in the arrangement. In contrast, the abnormal morphology in hippocampal CA1 area was significantly relieved by breviscapine in treated-group.(3) In the biochemical analysis, the activity of SOD in model group was decreased significantly (P<0.05), whereas MDA content was increased (P<0.05), compared with that in sham-operated group. However, the decrease of activity of SOD in cerebral cortex and hippocampus and the increase of the level of MDA were significantly improved by breviscapine (P<0.05). Conclusions: Breviscapine could enhance the learning and memory performance of vascular dementia and relieve the abnormal morphology induced by ischemia in hippocampal CA1 region. It also increases the activity of SOD and decreases content of MDA in cerebral cortex and hippocampus.PartⅡEffects of breviscapine on cultured rat cortical neuron injury induced by H2O2Objective: To investigate the action and mechanism of breviscapine on cultured rat cortical neuron injury induced by H2O2.Methods: The effect of breviscapine was observed by measurement of cell viability and calcium imaging.Results: (1) In cell viability assay, cell injury was induced by different concentration of H2O2 (5-500μM). H2O2 decreased cellular viability in a concentration-dependent manner. Pretreatment of breviscapine (6.25-100μg/L) significantly attenuated H2O2 (150μM)-induced cytotoxicity. The most effective concentration of breviscapine was 50μg/L, at which the cellular viability was 76.51±18.79% (P<0.05 vs H2O2 group). (2) In calcium imaging test, H2O2 at a concentration of 10mM induced a significant increase of [Ca2+]i. On the contrary, pretreatment of breviscapine 50μg/L for 24 h prevented the elevation of [Ca2+]i induced by H2O2. [Ca2+]i was significantly decreased by 29.10±0.08% relative to control (P<0.01) after pretreatment of breviscapine.Conclusions: Breviscapine could prevent the cultured rat cortical neurons from calcium overloading and cell death induced by H2O2.