Neuroprotective effect of escitalopram oxalate in rats with chronic hypoperfusion

Abstract

The neuroprotective effects of escitalopram oxalate in rats with chronic hypoperfusion and the possible mechanism were explored. 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, cell morphological changes in ischemic area and the plasma vascular endothelial growth factor (VEGF) were detected to explore the possible mechanisms. (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). It was concluded that escitalopram oxalate could significantly improve the learning and memory ability of the rats with chronic cerebral ischemia probably by the VEGF-mediated angiogenesis.

Keywords

escitalopram oxalate / chronic hypoperfusion / neuroprotection / mechanism / vascular endothelial growth factor

References

[1] GreeneJ, BanasrM, LeeB, et al. . Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. Neuropsychopharmacology, 2009, 34(11): 2459-2468 PMCID: 3694572 PMID: 19553916

[2] NowackaMM, ObuchowiczE. Vascular endothelial growth factor (VEGF) and its role in the central nervous system: a new element in the neurotrophic hypothesis of antidepressant drug action. Neuropeptides, 2012, 46(1): 1-10 PMID: 21719103

[3] ChenJ, SanbergPR, LiY, et al. . Intravenous administration of human umbilical cord blood reduces behavioral after stroke in rats. Stroke, 2001, 32(11): 2682-2688 PMID: 11692034

[4] BurnsMM, GreenbergDA. Antidepressants in the treatment of stroke. Expert Rev Neurother, 2010, 10(8): 1237-1241 PMID: 20662746

[5] Warner-SchmidtJL, DumanRS. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci USA, 2007, 104(11): 4647-4652 PMCID: 1838655 PMID: 17360578

[6] FaganSC, HessDC, HohnadelEJ, et al. . Targets for vascular protection after acute isehemic stroke. Stroke, 2004, 35(9): 2220-2225 PMID: 15284446

[7] KozakA, El-RemessyAB. Candesartan augments ischemia-induced proangiogenic state and results in sustained improvement after stroke. Stroke, 2009, 40(5): 1870-1876 PMCID: 2716175 PMID: 19265050

[8] NamieeinskaM, MareiniakK, NowakJZ. VEGF as an angiogenic neurotrophic and neuroprotective factor. Postepy Hig Med Dosw, 2005, 59(1): 573-583

[9] KongZH, LiuYM, ZhuJ, et al. . Effects of granulocyte colony-stimulating factor on brain nerve in chronic cerebral ischemic rats. Chin J Geriatrics (Chinese), 2013, 32(8): 882-885

[10] ZhangZG, ZhangL, JiangQ, et al. . Bone marrow derived endothelial progenitor cells participate in cerebral neovascularization after focal cerebral ischemia in the adult mouse. Circ Res, 2002, 90(3): 284-288 PMID: 11861416

[11] BrezunJM, DaszutaA. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience, 1999, 89(1): 999-1002 PMID: 10362289