Basic Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Physiology, School of Medicine, Medical Department of Physiology, Tehran University of Medical Sciences, Poorsina Ave, Tehran, Iran.
Cell Mol Neurobiol. 2022 May;42(4):1125-1139. doi: 10.1007/s10571-020-01004-z. Epub 2020 Nov 21.
The current study aimed to determine the protective effect of AY9944 related to Caveolin-1 and Claudin-5 role in lipid raft, which can rescue the blood-brain barrier from enhanced permeability. Therefore, in vivo analyses were performed following ischemia in normal, ischemic, and AY9944-treated animal groups. The results revealed that AY9944 reduced the infarct size, edema, and brain water content. The extravasation of Alb-Alexa 594 and biocytin-TMR was minimum in the AY9944-treated animals. The results showed a significant decrease in the expression level of Caveolin-1 over 8 h and 48 h and a remarkable increase in the level of Claudin-5 over 48 h following ischemia in AY9944-treated animals. Molecular docking simulation demonstrated that AY9944 exerts a possible protective role via attenuating the interaction of the Caveolin-1 and cholesterol in lipid raft. These findings point out that AY9944 plays a protective role in stroke by means of blood-brain barrier preservation. Proper neural function essentially needs a constant homeostatic brain environment which is provided by the blood-brain barrier. Rescuing blood-brain barrier from enhanced permeability via inducing the protective effect of AY9944 related to caveolin-1 and claudin-5 role in lipid raft was the aim of the current study.
本研究旨在确定 AY9944 通过对 Caveolin-1 和 Claudin-5 在脂筏中的作用，对血脑屏障通透性增强的保护作用。因此，在正常、缺血和 AY9944 处理的动物组中进行了体内分析。结果表明，AY9944 可减小梗死面积、脑水肿和脑含水量。在 AY9944 处理的动物中，Alb-Alexa 594 和 biocytin-TMR 的漏出最少。结果显示，在 AY9944 处理的动物中，缺血后 8 小时和 48 小时 Caveolin-1 的表达水平显著降低，48 小时 Claudin-5 的水平显著升高。分子对接模拟表明，AY9944 通过减弱脂筏中 Caveolin-1 和胆固醇的相互作用发挥可能的保护作用。这些发现表明，AY9944 通过保护血脑屏障发挥在中风中的保护作用。适当的神经功能需要一个由血脑屏障提供的恒定的脑内环境。通过诱导与 Caveolin-1 和 Claudin-5 在脂筏中的作用相关的 AY9944 的保护作用，从增强的通透性中拯救血脑屏障是本研究的目的。
