Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Stroke. 2012 Jun;43(6):1639-46. doi: 10.1161/STROKEAHA.111.643098. Epub 2012 Apr 5.
Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R).
Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1Rβ expression in the hippocampus was assessed by Western blotting.
The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1Rβ expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels.
The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats.
脑梗死是死亡或日常生活活动减少的主要原因。本研究旨在探讨常用抗血小板药物对与氧化应激标志物和胰岛素样生长因子 1 受体（IGF-1R）相关的卒中以及运动和认知功能的疗效。
从 8 到 10 周龄开始，将易发生卒中的自发性高血压大鼠用载体、阿司匹林、氯吡格雷和西洛他唑进行治疗。检查生理参数、局部脑血流和血清脂质。每周通过转棒和水迷宫任务评估运动和认知功能。通过免疫组织化学检查自发性梗死缺血边界区的脂质、蛋白质和 DNA 的氧化应激标志物以及海马中的 IGF-1R 阳性细胞比例，评估脑切片中的自发性梗死体积。通过 Western 印迹评估海马中的 IGF-1Rβ 表达。
抗血小板药物西洛他唑和氯吡格雷比阿司匹林更能减少自发性梗死体积。只有西洛他唑改善了运动和认知功能，使与记忆相关的 IGF-1R 阳性比例和海马中的 IGF-1Rβ 表达显著增加（P<0.05）。西洛他唑降低了易发生卒中的自发性高血压大鼠受影响神经元中的 4 种氧化应激标志物，而与血压、局部脑血流或血清脂质水平无关。
本研究结果表明，西洛他唑可能具有多效性作用，导致自发性梗死体积减少和运动及空间认知功能的保留。海马 CA1 区 IGF-1R 阳性细胞的增加可能部分解释了易发生卒中的自发性高血压大鼠空间认知功能的保留。
