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Pretreatment with bisoprolol and vitamin E alone or in combination provides neuroprotection against cerebral ischemia/reperfusion injury in rats

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Abstract

Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in the hippocampus, leading to severe impairment in behavior, learning, and memory functions. This study aimed to evaluate the neuroprotective effects of bisoprolol (biso) and vitamin E (vit E) treatment alone or in combination on cerebral ischemia/reperfusion (I/R) injury. A total of 30 male rats were divided randomly into five groups (n = 6), sham, I/R, I/R + biso, I/R + vit E, and I/R + biso+vit E. Cerebral I/R group underwent global ischemia by bilateral common carotid artery occlusion for 20 min. Treatment groups received drugs once daily intraperitoneally for 7 days before the I/R induction. Locomotive and cognitive behaviors were utilized by open-field and Morris water maze tests. After behavioral testing, the brain was removed and processed to evaluate cerebral infarct size, histopathologic changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) level. In I/R group tissue MDA and MPO levels and cerebral infarct size were significantly increased in comparison with the sham group. Furthermore, significant deficits were observed in locomotion and spatial memory after I/R. The areas of cerebral infarction, MPO, and MDA levels in biso, vit E, and combination group were significantly reduced compared with I/R group. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration in all treated groups with the most profound reduction in the combination group. According to the behavioral tests, administration of biso and/or vit E protected locomotive ability and improved spatial memory after cerebral I/R. Our findings show that biso and vit E have beneficial effects against the I/R injury and due to their synergistic effects when administered in combination, may have a more pronounced protective effect on the cerebral I/R injury.

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Funding

This research has been supported by Urmia University of Medical Sciences and Health Services (grant number: IR. UMSU 2595).

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  1. Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, PO Box 5715799313, Urmia, Iran

    Chiman Salehi, Monireh Seiiedy, Hamid Soraya, Farzaneh Fazli & Morteza Ghasemnejad-Berenji

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  1. Chiman Salehi
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  2. Monireh Seiiedy
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  3. Hamid Soraya
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The authors declare that all data were generated in-house and that no paper mill was used. M Ghasemnejad-Berenji and Hamid Soraya: study design, analysis of the data, revised the article, and funding acquisition. Chiman Salehi: investigation, literature review, and writing the original draft of the article. Monireh Seiiedy: literature review and writing manuscript. Farzaneh Fazli: performed the behavioral analyses. All authors contributed substantially to this work and approved the final manuscript.

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Correspondence to Hamid Soraya or Morteza Ghasemnejad-Berenji.

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All procedures were conducted in accordance with the accepted principles for the care and use of laboratory animals and were approved by the animal ethics committee of Urmia University of Medical Sciences (IR.UMSU.REC.1397.328).

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Salehi, C., Seiiedy, M., Soraya, H. et al. Pretreatment with bisoprolol and vitamin E alone or in combination provides neuroprotection against cerebral ischemia/reperfusion injury in rats. Naunyn-Schmiedeberg's Arch Pharmacol 394, 685–695 (2021). https://doi.org/10.1007/s00210-020-02007-9

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