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Neuroprotective Effects of Chemerin on a Mouse Stroke Model: Behavioral and Molecular Dimensions

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Abstract

The present study was conducted to investigate the effects of different doses of recombinant human Chemerin (rhChemerin) on brain damage, spatial memory, blood–brain barrier (BBB) disruption and cellular and molecular mechanisms in a mouse stroke model. The mouse stroke model was developed by blocking the middle cerebral artery for 1 h and performing reperfusion for 23 h. Immediately, one and three hours after the stroke, 200, 400 and 800 ng/mouse of intranasal rhChemerin was administered. Neuronal and BBB damage, spatial memory and neurological performance were examined 24 h after the stroke. Western blotting and immunofluorescence were utilized to determine the effects of rhChemerin on the expressions of nuclear factor kappa B (NF-κB), pro-inflammatory cytokines such as TNF-α and IL-1β, anti-inflammatory cytokines such as IL-10 and TGF-β and vascular endothelial growth factor (VEGF). Administering 400 and 800 ng/mouse of rhChemerin in the mice immediately and one hour after ischemia minimized the infarct size, BBB opening, spatial memory and neurological impairment (P < 0.001). Furthermore, 800 ng/mouse of rhChemerin significantly diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive (apoptotic) cells, suppressed the expressions of NF-kB, TNF-α and IL-1β and upregulated IL-10 and VEGF in the cortex and hippocampus of the mice. The present findings showed that rhChemerin administered immediately and one hour after stroke alleviates neuronal and BBB injures and improves spatial memory. These effects of rhChemerin may be mediated by inhibiting inflammatory pathways and apoptotic machinery.

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Data Availability

The data are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Dr. Hamid Madanchi for assisting in some technical procedures. We also thank from Prof. Ali Rashidy-Pour for his help in editing parts of the manuscript.

Funding

This work was supported by a research grant from Vice Chancellor for Research of the Semnan University of Medical Sciences (Grant Number: 1538).

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Authors and Affiliations

  1. Research Center and Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Azam Abareshi, Shahein Momenabadi, Abbas Ali Vafaei & Abedin Vakili

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

    Azam Abareshi, Shahein Momenabadi, Abbas Ali Vafaei & Abedin Vakili

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

    Ahmad Reza Bandegi

Authors
  1. Azam Abareshi
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  2. Shahein Momenabadi
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  3. Abbas Ali Vafaei
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  4. Ahmad Reza Bandegi
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  5. Abedin Vakili
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Contributions

AV contributed to conception and design of the research. AA; SM; AV and AAV contributed to all experimental work, data and statistical analysis, and interpretation of data. ARB contributed to measuring BBB permeability. AA and AV contributed extensively to interpretation of the data and the conclusion. AV was responsible for overall supervision. AV did molecular experiments in Basic Medical Science Research, Histogenotech Company, Tehran, Iran. All authors read and approved the final version of the manuscript.

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Correspondence to Abedin Vakili.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Abareshi, A., Momenabadi, S., Vafaei, A.A. et al. Neuroprotective Effects of Chemerin on a Mouse Stroke Model: Behavioral and Molecular Dimensions. Neurochem Res 46, 3301–3313 (2021). https://doi.org/10.1007/s11064-021-03432-9

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  • DOI: https://doi.org/10.1007/s11064-021-03432-9

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