Targeting Caveolin-1 and Claudin-5 with AY9944, Improve Blood–Brain Barrier Permeability; Computational Simulation and Experimental Study

• Published in: Cellular and molecular neurobiology 2022-05, Vol.42 (4), p.1125-1139
• Main Authors: Gholami, Leila, Jokar, Safura, Fatahi, Yousef, Samandari, Hedayat, Hamzehalipour Almaki, Javad, Hosseini, Marjan, Parviz, Mohsen
• Format: Article
• Language: English
• Subjects: Animals; Biocytin; Biomedical and Life Sciences; Biomedicine; Blood-Brain Barrier; Caveolin; Caveolin 1 - metabolism; Caveolin-1; Cell Biology; Cholesterol; Claudin-5 - metabolism; Computational neuroscience; Edema; Extravasation; Ischemia; Lipids; Membrane permeability; Molecular Docking Simulation; Neurobiology; Neurosciences; Original Research; Permeability; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride - metabolism; trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride - pharmacology; Water content
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-020-01004-z

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.