Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
CNS Neurosci Ther. 2012 Apr;18(4):343-9. doi: 10.1111/j.1755-5949.2012.00302.x.
Stroke is the second most common cause of death and a major cause of disability worldwide. Risperidone is an atypical antipsychotic drug that may increase the risk of stroke. The present work examined whether risperidone enhances the vulnerability to stroke in hypertensive rats and the potential mechanisms underlying such action.
Experiment 1: Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHRs) and stroke-prone SHRs (SHR-SPs) were treated with risperidone (0.8 and 2.4 mg/kg/d) or vehicle for 30 consecutive days. Tissue damage in response to middle cerebral artery occlusion (MCAO) was measured microscopically. The activity of superoxide dismutase, glutathione peroxidase, the levels of malondialdehyde were also determined. Experiment 2: Survival data were recorded in SHR-SPs that received daily risperidone perpetually. Experiment 3: Effect of risperidone on interleukin-6 and tumor necrosis factor-α was examined in quiescent or LPS-activated cortical microglias from WKY rats. Experiment 4: Potential damage of risperidone exposure to neurons was examined in primary neuronal culture obtained from WKY rats, SHRs, and SHR-SPs.
Risperidone increased infarct areas upon MCAO in SHR-SPs and SHRs, but not in WKY rats. Survival time in SHR-SPs was shortened by risperidone. Apoptosis was augmented by risperidone through enhanced Bax. Risperidone also increased endothelial injury.
Risperidone enhances the vulnerability to stroke in hypertensive rats through increasing neuronal apoptosis and endothelial injury.
中风是全球范围内第二大致死原因和主要致残原因。利培酮是一种非典型抗精神病药物，可能会增加中风风险。本研究旨在探讨利培酮是否会增加高血压大鼠发生中风的易感性，以及这种作用的潜在机制。
实验 1：Wistar-Kyoto（WKY）大鼠、自发性高血压大鼠（SHR）和易发性中风 SHR（SHR-SP）连续 30 天给予利培酮（0.8 和 2.4mg/kg/d）或载体处理。用显微镜测量大脑中动脉闭塞（MCAO）后的组织损伤。还测定了超氧化物歧化酶、谷胱甘肽过氧化物酶的活性以及丙二醛的水平。实验 2：记录接受利培酮持续治疗的 SHR-SP 的存活数据。实验 3：在 WKY 大鼠的静止或 LPS 激活的皮质小胶质细胞中检测利培酮对白细胞介素-6 和肿瘤坏死因子-α的影响。实验 4：在 WKY 大鼠、SHR 和 SHR-SP 的原代神经元培养物中检测利培酮暴露对神经元的潜在损伤。
利培酮增加了 SHR-SP 和 SHR 中 MCAO 后的梗死面积，但在 WKY 大鼠中没有增加。利培酮缩短了 SHR-SP 的存活时间。利培酮通过增强 Bax 增加了细胞凋亡。利培酮还增加了内皮损伤。
利培酮通过增加神经元凋亡和内皮损伤，增加了高血压大鼠中风的易感性。
