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熔融固体脂质微粒诱导的短暂性脑缺血发作可保护大鼠大脑免受永久性局灶性缺血损伤。

Transient ischemic attack induced by melted solid lipid microparticles protects rat brains from permanent focal ischemia.

作者信息

Tsai M-J, Kuo Y-M, Tsai Y-H

机构信息

Department of Neurology, China Medical University Hospital, Taichung, Taiwan; School of Medicine, Medical College, China Medical University, Taichung, Taiwan; Department of Neurology, Tainan Municipal An-Nan Hospital-China Medical University, Tainan, Taiwan.

Department of Cell Biology and Anatomy, National Cheng Kung University, Tainan, Taiwan.

出版信息

Neuroscience. 2014 Sep 5;275:136-45. doi: 10.1016/j.neuroscience.2014.06.014. Epub 2014 Jun 14.

Abstract

This study aims to develop a transient ischemic attack (TIA) model in conscious animals and uses this model to investigate the effect of TIA on subsequent permanent ischemia. TIA was induced by injecting designed temperature-sensitive melted solid lipid microparticles with a melting point around body temperature into male Wistar rats via arterial cannulation. Neurologic deficit was monitored immediately after the injection without anesthesia. According to the clinical definition of TIA, rats were divided into neurologic symptom durations <24-h, 24-48-h and ≥48-h groups. The lipid microparticle-induced infarct volumes were small in the <24-h and 24-48-h groups, while the volumes were five times larger in the ≥48-h group. Permanent ischemic stroke was induced 3d after the induction of TIA by injecting a different kind of embolic particle manufactured by blending chitin and PLGA. The <24-h group had less severe neurologic deficits and smaller infarct volumes than that of 24-48-h and control (without prior lipid microparticle treatment) rats. Taken together, we successfully develop a TIA animal model which allows us to monitor the neurologic deficit in real-time. By adopting this model, we validate that TIA (<24h) preconditioning protects the brain from subsequent permanent ischemic stroke.

摘要

本研究旨在建立清醒动物短暂性脑缺血发作(TIA)模型,并利用该模型研究TIA对随后永久性缺血的影响。通过动脉插管将熔点接近体温的特制温度敏感型熔融固体脂质微粒注射到雄性Wistar大鼠体内,诱导TIA。注射后在未麻醉状态下立即监测神经功能缺损情况。根据TIA的临床定义,将大鼠分为神经症状持续时间<24小时、24 - 48小时和≥48小时组。在<24小时和24 - 48小时组中,脂质微粒诱导的梗死体积较小,而在≥48小时组中,梗死体积大五倍。在TIA诱导后3天,通过注射由几丁质和聚乳酸 - 羟基乙酸共聚物(PLGA)混合制成的另一种栓塞微粒诱导永久性缺血性卒中。<24小时组的神经功能缺损比24 - 48小时组和对照组(未预先进行脂质微粒处理)的大鼠轻,梗死体积也更小。综上所述,我们成功建立了一个TIA动物模型,该模型使我们能够实时监测神经功能缺损情况。通过采用该模型,我们验证了TIA(<24小时)预处理可保护大脑免受随后的永久性缺血性卒中的影响。

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