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Oxytocin Reduces Brain Injury and Maintains Blood–Brain Barrier Integrity After Ischemic Stroke in Mice

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Abstract

The present study was designed to determine the effect of different doses of oxytocin (OXT) on neuronal injury, spatial memory, blood-brain barrier (BBB) integrity and to explore possible underlying molecular mechanisms in the early stage of stroke in mice. Stroke model was generated by middle cerebral artery occlusion (MCAO) for 60 min and 24 h reperfusion in mice. OXT at doses of 1, 2, 4 and 8 IU/per mouse was administrated intranasally at the beginning of brain ischemia. Brain injury, BBB integrity, and spatial memory were evaluated by standard methods. Changes in the expression of nuclear factor-kappa B (NF-κB), and TUNEL positive cell were detected by immunohistochemistry. The levels of vascular endothelial growth factor (VEGF), aquaporin-4 (AQP4) and brain-derived neurotrophic factor (BDNF) proteins were determined by western blotting and ELISA methods. OXT at doses of 4 and 8 IU/per mouse reduced the infarct size by 42% and 52%, respectively, and improved spatial memory function (p < 0.001). OXT (8 IU/per mouse) significantly reduced brain edema, BBB disruption and upregulated the AQP4 expression (p < 0.001). Finally, OXT significantly diminished the number of apoptotic, NF-κB positive cells and enhanced the expression of BDNF and VEGF proteins in the brain tissue (p < 0.001). These findings provide important evidences that OXT significantly suppresses neuronal damage in the early stage of stroke by inhibiting apoptotic and NF-κB signaling pathway, increasing the expression of VEGF, AQP4 and BDNF proteins and reducing the BBB leakage.

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Acknowledgements

This study was funded by a research grant from Vice Chancellor for Research of the Semnan University of Medical Sciences (Grant Number: 1355). We thanks from Prof. Ali Rashidy-Pour for valuable comments and correction of manuscript and Mehrnoush Rahmani for help in doing of spatial memory evaluation. We also thank for some technical assistance provided by Reza Nasr form the Department of Biotechnology, Semnan University of Medical Sciences.

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Authors and Affiliations

  1. Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Shahein Momenabadi, Abbas Ali Vafaei, Mahdi Zahedi-Khorasani & Abedin Vakili

  2. Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Shahein Momenabadi, Abbas Ali Vafaei, Mahdi Zahedi-Khorasani & Abedin Vakili

  3. Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Ahmad Reza Bandegi

  4. Basic Medical Science Research, Histogenotech Company, Tehran, Iran

    Zohreh Mazaheri

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  1. Shahein Momenabadi
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  2. Abbas Ali Vafaei
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Correspondence to Abedin Vakili.

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All of procedures performed in this studies involving animals were in accordance with institutional animal care committee for animal surgery and ethical international guidelines for the care and use of laboratory animals. Research procedure and protocols were approved by the SUMS institutional Committee of Research Ethics (Ethical Code Number: IR.SUMUMS.REC. 1396.241).

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Momenabadi, S., Vafaei, A.A., Bandegi, A.R. et al. Oxytocin Reduces Brain Injury and Maintains Blood–Brain Barrier Integrity After Ischemic Stroke in Mice. Neuromol Med 22, 557–571 (2020). https://doi.org/10.1007/s12017-020-08613-3

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