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Apelin-13 Protects the Brain Against Ischemic Reperfusion Injury and Cerebral Edema in a Transient Model of Focal Cerebral Ischemia

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Abstract

The adipocytokine apelin is a peptide that was isolated from a bovine stomach for the first time. This peptide and its receptor are abundantly expressed in the nervous and cardiovascular systems. According to previous studies, apelin-13 protects cardiomyocytes from ischemic injury as well as apoptosis. In addition, this peptide has a neuroprotective effect on hippocampal and cultured mouse cortical neurons against NMDA receptor-mediated excitotoxicity. The present study was conducted to determine whether apelin-13 provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and apelin-13 at doses of 25, 50, and 100 μg were injected intracerebroventriculary (ICV) at the beginning of ischemia. Infarct volume ,brain edema, motor dysfunction, and apoptosis were assessed 24 h after MCAO. Treatment with apelin-13 at doses of 50 and 100 μg ICV markedly reduced total infarct volumes by 45 and 55 %, respectively (P < 0.001), but injection of apelin at lower dose (25 μg) did not change infarct volume significantly (P > 0.05). In addition, apelin-13 at doses of 50 and 100 μg reduced brain edema (P < 0.001) and inhibited apoptosis by decreasing caspase-3 activation (P < 0.001). Apelin-13 did not significantly change neurological dysfunction (P > 0.05).

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Acknowledgments

This study was part of a Ph.D. thesis supported by Tehran University of Medical Sciences grant number 1032p.

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Authors and Affiliations

  1. Physiology Research Center and Physiology Department, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Mehdi Khaksari, Nahid Aboutaleb & Farinaz Nasirinezhad

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

    Abedin Vakili

  3. Department of Pathology and Oncopathology Research Centre, Tehran University of Medical Sciences, Tehran, Iran

    Zahra Madjd

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  1. Mehdi Khaksari
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  2. Nahid Aboutaleb
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  3. Farinaz Nasirinezhad
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  4. Abedin Vakili
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Correspondence to Nahid Aboutaleb.

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Khaksari, M., Aboutaleb, N., Nasirinezhad, F. et al. Apelin-13 Protects the Brain Against Ischemic Reperfusion Injury and Cerebral Edema in a Transient Model of Focal Cerebral Ischemia. J Mol Neurosci 48, 201–208 (2012). https://doi.org/10.1007/s12031-012-9808-3

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  • DOI: https://doi.org/10.1007/s12031-012-9808-3

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