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Targeting Caveolin-1 and Claudin-5 With Ay9944, Improve Blood–Brain Barrier Permeability; Computational Simulation and Experimental Study Publisher Pubmed



Gholami L1, 2 ; Jokar S3 ; Fatahi Y4, 5, 6 ; Samandari H1 ; Hamzehalipour Almaki J5, 7 ; Hosseini M1 ; Parviz M1, 2
Authors

Source: Cellular and Molecular Neurobiology Published:2022


Abstract

Abstract: 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. Graphic Abstract: 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.[Figure not available: see fulltext.] © 2020, Springer Science+Business Media, LLC, part of Springer Nature.
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