title: Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia.
abstract: Free radicals are known to cause secondary neuronal damage in cerebral ischemia/reperfusion (I/R). We investigated here the neuroprotective effect of resveratrol, a potent antioxidant present in grape seed, against cerebral I/R-induced mitochondrial dysfunctions in hippocampus. Transient rat middle cerebral artery occlusion (MCAO) model of brain ischemia was used to induce brain infarction. Resveratrol (10(-7) g/kg) was given twice intravenously: 15 min pre-occlusion and at the time of reperfusion (2 h post-occlusion). Resveratrol significantly restored ATP content and the activity of mitochondrial respiratory complexes in resveratrol treated group which were severely altered in MCAO group. Western blot analysis showed a marked decrease in cytochrome c release as a result of resveratrol treatment. Electrophoretic migration of hippocampal genomic DNA showed a marked decrease in DNA fragmentation after resveratrol treatment. Notably, expression of Hsp70 and metallothionein (MT) was significantly higher in MCAO group but their expression was more significant in resveratrol treated group. The status of mitochondrial glutathione (GSH), glucose 6-phosphate dehydrogenase (G6-PD) and serum lactate dehydrogenase (LDH) was restored by resveratrol treatment with a significant decrease in mitochondrial lipid peroxidation (LPO), protein carbonyl and intracellular H(2)O(2) content. Resveratrol significantly improved neurological deficits assessed by different scoring methods. Also, the brain infarct volume and brain edema were significantly reduced. Histological analysis of CA1 hippocampal region revealed that resveratrol treatment diminished intercellular and pericellular edema and glial cell infiltration. The findings of this study highlight the ability of resveratrol in anatomical and functional preservation of ischemic neurovascular units and its relevance in the treatment of ischemic stroke.
authors.affiliation: Neurotoxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
authors.forename: Seema
authors.initials: S
authors.lastname: Yousuf
authors.forename: Fahim
authors.initials: F
authors.lastname: Atif
authors.forename: Muzamil
authors.initials: M
authors.lastname: Ahmad
authors.forename: Nasrul
authors.initials: N
authors.lastname: Hoda
authors.forename: Tauheed
authors.initials: T
authors.lastname: Ishrat
authors.forename: Badruzaman
authors.initials: B
authors.lastname: Khan
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Islam
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology*; D016923:Cell Death / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy; D045022:Lactate Dehydrogenases / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D013267:Stilbenes; D000255:Adenosine Triphosphate; D045304:Cytochromes c; D008668:Metallothionein; D006861:Hydrogen Peroxide; D045022:Lactate Dehydrogenases; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D000077185:Resveratrol