Estradiol modulates post-ischemic cerebral vascular remodeling and improves long-term functional outcome in a rat model of stroke

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• 作者：Agnieszka A. Ardelt^a ; ^{aardelt@neurology.bsd.uchicago.edu} ; Randall S. Carpenter^a ; Merryl R. Lobo^b ; Huadong Zeng^c ; Rajanikant B. Solanki^a ; An Zhang^a ; Piotr Kulesza^d ; Martin M. Pike^b
• 关键词：Stroke ; Cerebral ischemia ; Neurorepair ; Rat ; Middle cerebral artery occlusion ; Estradiol ; Angiogenesis ; Magnetic resonance imaging ; Functional recovery
• 刊名：Brain Research
• 出版年：2012
• 期刊代码：8_00068993
• 类别：neu
• 出版时间：21 June, 2012
• 卷：1461
• 期：Complete
• 页码：76-86
• 文件大小：1437 K

摘要

We previously observed that 17尾-estradiol (E2) augments ischemic borderzone vascular density 10 days after focal cerebral ischemia-reperfusion in rats. We now evaluated the effect of E2 on vascular remodeling, lesional characteristics, and motor recovery up to 30 days after injury. Peri-lesional vascular density in tissue sections from rats treated with 0.72 mg E2 pellets was higher compared to 0.18 mg E2 pellets or placebo (P) pellets: vascular density index, 1.9 卤 0.2 (0.72 mg E2) vs. 1.4 卤 0.2 (0.18 mg E2) vs. 1.5 卤 0.4 (P), p = 0.01. This was consistent with perfusion magnetic resonance imaging (MRI) measurements of lesional relative cerebral blood flow (rCBF): 1.89 卤 0.32 (0.72 mg E2) vs. 1.32 卤 0.19 (P), p = 0.04. Post-ischemic angiogenesis occurred in P-treated as well as E2-treated rats. There was no treatment-related effect on lesional size, but lesional tissue was better preserved in E2-treated rats: cystic component as a%of total lesion, 30 卤 12 (0.72 mg E2) vs. 29 卤 17 (0.18 mg E2) vs. 61 卤 29 (P), p = 0.008. Three weeks after right middle cerebral artery territory injury, rats treated with 0.72 mg E2 pellets used the left forelimb more than P-treated or 0.18 mg E2-treated rats: limb use asymmetry score, 0.09 卤 0.43 (0.72 mg E2) vs. 0.54 卤 0.12 (0.18 mg E2) vs. 0.54 卤 0.40 (P), p = 0.05. We conclude that treatment with 0.72 mg E2 pellets beginning one week prior to ischemia/reperfusion and continuing through the one-month recovery period results in augmentation of lesional vascularity and perfusion, as well as improved motor recovery.