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Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat

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Abstract

Stroke is a life-threatening disease with major cause of mortality and morbidity worldwide. The neuronal damage following cerebral ischemia is a serious risk to stroke patients. Oxidative stress and apoptotic damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The objective of this study was to test the hypothesis that administration of edaravone (Edv) maintains antioxidant status in brain, improves the cholinergic dysfunction and suppresses the progression of apoptosis response in rat. To test this hypothesis, male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) of 2 h followed by reperfusion for 22 h. Edv was administered (10 mg/kg bwt) intraperitoneally 30 min before the onset of ischemia and 1 h after reperfusion. After reperfusion, rats were tested for neurobehavioral activities and were sacrificed for the infarct volume, estimation of oxidative damage markers. Edv treatment significantly reduced ischemic lesion volume, improved neurological deficits, contended oxidative loads, and suppressed apoptotic damage. In conclusion, treatment with Edv ameliorated the neurological and histological outcomes with elevated endogenous anti-oxidants status as well as reduced induction of apoptotic responses in MCA occluded rat. We theorized that Edv is among the pharmacological agents that reduce free radicals and its associated cholinergic dysfunction and apoptotic damage and have been found to limit the extent of brain damage following stroke.

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Acknowledgments

Authors are thankful to the Department of Ayurveda, Yoga and Naturalpathy, Unani, Siddha and Homeopath (AYUSH), Ministry of Health and Family Welfare, Government of India, New Delhi for financial assistance. The authors wish to thanks Mr. Dharamvir Singh for his assistance.

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Authors and Affiliations

  1. Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology (Fund for the Improvement of Science and Technology-DST and Special Assistance Programme-UGC Sponsored), Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, 110062, India

    Ajmal Ahmad, Mohd. Moshahid Khan, Hayate Javed, Syed Shadab Raza, Tauheed Ishrat, M. Badruzzaman Khan & Fakhrul Islam

  2. Neuroscience and Toxicology Unit, Faculty of Pharmacy, Jazan University, Jazan, Kingdom of Saudi Arabia

    Mohammed M. Safhi & Fakhrul Islam

  3. Department of Neurology, Georgia Health Sciences University, Augusta, GA, 30912, USA

    Ajmal Ahmad

  4. Department of Neurology, Carver College of Medicine, University of Iowa, Iowa City, IA, USA

    Mohd. Moshahid Khan

  5. Department of Clinical and Administrative Pharmacy, University of Georgia, Augusta, GA, 30912, USA

    Tauheed Ishrat

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  1. Ajmal Ahmad
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Correspondence to Fakhrul Islam.

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Ahmad, A., Moshahid Khan, M., Javed, H. et al. Edaravone ameliorates oxidative stress associated cholinergic dysfunction and limits apoptotic response following focal cerebral ischemia in rat. Mol Cell Biochem 367, 215–225 (2012). https://doi.org/10.1007/s11010-012-1335-6

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  • DOI: https://doi.org/10.1007/s11010-012-1335-6

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