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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
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Authors Affiliations
  1. 1. Basic Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Physiology, School of Medicine, Medical Department of Physiology, Tehran University of Medical Sciences, Poorsina Ave, Tehran, Iran
  3. 3. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Universal Scientific Education and Research Network (USERN), Tehran, Iran
  7. 7. Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, Johor Bahru, Johor, Skudai, 81110 UTM, Malaysia

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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