Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia

Seema Yousuf, Fahim Atif, Muzamil Ahmad, Nasrul Hoda, Tauheed Ishrat, Badruzaman Khan, Fakhrul Islam

Research output: Contribution to journalArticle

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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 H2O2 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.

Original languageEnglish (US)
Pages (from-to)242-253
Number of pages12
JournalBrain Research
Volume1250
DOIs
StatePublished - Jan 23 2009
Externally publishedYes

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Neuroprotective Agents
Brain Ischemia
Cell Death
Middle Cerebral Artery Infarction
Reperfusion
resveratrol
Brain Infarction
Hippocampal CA1 Region
Metallothionein
Glucosephosphate Dehydrogenase
Brain Edema
Vitis
DNA Fragmentation
Cytochromes c
L-Lactate Dehydrogenase
Neuroglia
Lipid Peroxidation
Free Radicals
Glutathione
Hippocampus

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. / Yousuf, Seema; Atif, Fahim; Ahmad, Muzamil; Hoda, Nasrul; Ishrat, Tauheed; Khan, Badruzaman; Islam, Fakhrul.

In: Brain Research, Vol. 1250, 23.01.2009, p. 242-253.

Research output: Contribution to journalArticle

Yousuf, Seema ; Atif, Fahim ; Ahmad, Muzamil ; Hoda, Nasrul ; Ishrat, Tauheed ; Khan, Badruzaman ; Islam, Fakhrul. / Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. In: Brain Research. 2009 ; Vol. 1250. pp. 242-253.
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