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

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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.

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Acknowledgements

This research was a part of a Ph.D. thesis and supported by Basic Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.

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Authors and Affiliations

  1. Basic Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

    Leila Gholami, Hedayat Samandari, Marjan Hosseini & Mohsen Parviz

  2. Department of Physiology, School of Medicine, Medical Department of Physiology, Tehran University of Medical Sciences, Poorsina Ave, Tehran, Iran

    Leila Gholami & Mohsen Parviz

  3. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Safura Jokar

  4. Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Yousef Fatahi

  5. Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Yousef Fatahi & Javad Hamzehalipour Almaki

  6. Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Yousef Fatahi

  7. Institute of Bioproduct Development (IBD), Universiti Teknologi Malaysia, Johor Bahru, 81110 UTM, Skudai, Johor, Malaysia

    Javad Hamzehalipour Almaki

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  1. Leila Gholami
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Gholami, L., Jokar, S., Fatahi, Y. et al. Targeting Caveolin-1 and Claudin-5 with AY9944, Improve Blood–Brain Barrier Permeability; Computational Simulation and Experimental Study. Cell Mol Neurobiol 42, 1125–1139 (2022). https://doi.org/10.1007/s10571-020-01004-z

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