title: Alteration in bioenergetic regulators, SirT1 and Parp1 expression precedes oxidative stress in rats subjected to transient cerebral focal ischemia: molecular and histopathologic evidences.
abstract: The present study was undertaken to identify the time-dependent changes in bioenergetic regulators and oxidative stress markers levels and also to ascertain which occurs early in focal cerebral ischemia. The status of bioenergetic regulators (nicotinamide adenine dinucleotide, Silent information regulator Transporter 1 (SirT1) and Poly adenosine diphosphate--ribose polymerase 1 (Parp1)) and oxidative stress markers' (lipid peroxidation and nitric oxide) levels along with excitatory neurochemical glutamate, neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and caspase 3 at various durations of reperfusion viz 0, 1, 6, 24, 72, and 166 hours was investigated in rats subjected to 2 hours of middle cerebral artery occlusion. Six hours after reperfusion, a significant downregulation in SirT1 and upregulation in Parp1 expressions were observed in striatal region of ischemic-reperfused rats compared with ischemic rats. Peak elevation in glutamate content was recorded at 72 hours, and maximum level of lipid peroxidation and nitric oxide contents were observed at 166 hours. A significant decrease in NeuN and increase in GFAP-positive cells were observed at 24 and 72 hours, respectively, in cortical, striatal, and hippocampal regions. These data reveal that change in bioenergetic regulators occurs earlier than excitotoxicity and oxidative stress in cerebral stroke. From the data, it can also be inferred that appropriate therapeutic intervention, that is, bioenergetic modulators at early period and either glutamatergic and/or antioxidant therapy at delayed period may yield a better therapeutic outcome.
authors.affiliation: Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu, India; Department of Biochemistry, PRIST University, Vallam, Tamilnadu, India.
authors.forename: Periyathambi
authors.initials: P
authors.lastname: Kalaivani
authors.affiliation: Department of Biochemistry, Sri Ramachandra University, Chennai, Tamil Nadu, India.
authors.forename: Murugan
authors.initials: M
authors.lastname: Ganesh
authors.affiliation: Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu, India.
authors.forename: Sekar
authors.initials: S
authors.lastname: Sathiya
authors.affiliation: Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu, India.
authors.forename: Vijayan
authors.initials: V
authors.lastname: Ranju
authors.affiliation: Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu, India.
authors.forename: Veeraragavan
authors.initials: V
authors.lastname: Gayathiri
authors.affiliation: Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai, Tamil Nadu, India. Electronic address: ceftpublications@gmail.com.
authors.forename: Chidambaram
authors.initials: C
authors.lastname: Saravana Babu
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology; D003342:Corpus Striatum / Q000166:cytology; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D051381:Rats; D015424:Reperfusion; D056564:Sirtuin 1 / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D005904:Glial Fibrillary Acidic Protein; D009569:Nitric Oxide; D018698:Glutamic Acid; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; C488368:Sirt1 protein, rat; D056564:Sirtuin 1
keywords: Parp1; SirT1; bioenergetics; focal cerebral ischemia; oxidative stress