Experimental Study For Neuroprotection Of Escitalopram Oxalate On Acute And Chronic Cerebral Ischemia And Its Possible Mechanism In Rats

Objective:The neuroprotective effects of escitalopram oxalate in rats with acute cerebral ischemia and chronic hypoperfusion and the possible mechanism were explored preliminarily.Methods:Part One:Focal middle cerebral artery occlusion model (MCAO) was prepared and given escitalopram oxalate (experimental group) or PBS (control group) after 2 hours. Two weeks after the operation, neurological deficit of rats in each group were evaluated by modified neurological severity score (mNSS) scale. The cell proloferation,three-dimensional vascular distribution, the number of apoptotic cells,cell morphological changes in ischemic area and the plasma vascular endothelial growth factor (VEGF) were detected to explore the possible mechanisms.Part Two:Chronic hypoperfusion (2-VO) model was prepared and given escitalopram oxalate (experimental group) or PBS (control group) after 6 weeks. Eight weeks after the operation, Morris water maze test was carried out to evaluate the learning and memory ability of the rats. The cell proliferation, three-dimensional vascular distribution in ischemic area and the plasma vascular endothelial growth factor (VEGF) were detected to explore the possible mechanisms.Results:Part One:(1)The mNSS in the experimental group was significantly lower than that in the control group after 2 weeks (P<0.05)(2) Cerebrovascular confocal detection results showed that the inside diameter of capillaries was significantly less in the experimental group than in the control group (P<0.05); the vascular density was significantly increased in the experimental group (P<0.01) and the total area of capillaries was also significantly increased in the experimental group as compared with the control group (P<0.05)(3) There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group (P<0.05)(4)The number of apoptotic cells in the experimental group was significantly less than that in the control group (P<0.05)(5)The observation of transmission electron mictoscope showed that the infalmmatory edema in the experimental group was significantly reduced compare to the control group (P<0.05) (6) VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group (P<0.05).Part Two:(1) Morris water maze test showed that the escape latency in the experimental group was significantly shorter than in the control group, while the first quadrant swimming time in the experimental group was significantly longer than the control group (both P<0.01).(2) Cerebrovascular confocal detection results showed that the inside diameter of capillaries was significantly less in the experimental group than in the control group; the vascular density was significantly increased in the experimental group and the total area of capillaries was also significantly increased in the experimental group as compared with the control group.(3) There was statistically significant difference in BrdU-positive cells in the ischemic brain tissue between the experimental group and the control group (P=0.003<0.01).(4) VEGF concentrations in the plasma and the ischemic area were higher in the experimental group than in the control group (P<0.05).Conclusion:It was concluded that escitalopram oxalate could significantly improve the neural functional recovery of the rats with acute and chronic cerebral ischemia probably by the VEGF-mediated angiogenesis.