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

• Published in: Molecular and cellular biochemistry Vol. 367; no. 1-2; pp. 215 - 225
• Main Authors: Ahmad, Ajmal, Moshahid Khan, Mohd, Javed, Hayate, Raza, Syed Shadab, Ishrat, Tauheed, Badruzzaman Khan, M., Safhi, Mohammed M., Islam, Fakhrul
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.08.2012; Springer; Springer Nature B.V
• Subjects: Animals; Antioxidants; Antipyrine - analogs & derivatives; Antipyrine - pharmacology; Antipyrine - therapeutic use; Apoptosis; Apoptosis - drug effects; Basal Ganglia - drug effects; Basal Ganglia - enzymology; Basal Ganglia - pathology; Biochemistry; Biomedical and Life Sciences; Cardiology; Caspase 3 - metabolism; Cerebral ischemia; Choline O-Acetyltransferase - metabolism; Cholinergic Neurons - metabolism; Cholinergic Neurons - pathology; Free Radical Scavengers - pharmacology; Free Radical Scavengers - therapeutic use; Glucosephosphate Dehydrogenase - metabolism; Glutathione - metabolism; Glutathione Peroxidase - metabolism; Glutathione Reductase - metabolism; Glutathione Transferase - metabolism; Health aspects; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Ischemic Attack, Transient - drug therapy; Ischemic Attack, Transient - metabolism; Ischemic Attack, Transient - pathology; Life Sciences; Male; Medical Biochemistry; Motor Activity - drug effects; Oncology; Oxidative stress; Oxidative Stress - drug effects; Protein Carbonylation - drug effects; Proto-Oncogene Proteins c-bcl-2 - metabolism; Rats; Rats, Wistar; Rodents; Rotarod Performance Test; Stroke; Thiobarbituric Acid Reactive Substances - metabolism; Oxidative stress; Neuroprotection; Cerebral ischemia; Antioxidant; Apoptosis
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-012-1335-6

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.