title: Resveratrol Treatment after Status Epilepticus Restrains Neurodegeneration and Abnormal Neurogenesis with Suppression of Oxidative Stress and Inflammation.
abstract: Antiepileptic drug therapy, though beneficial for restraining seizures, cannot thwart status epilepticus (SE) induced neurodegeneration or down-stream detrimental changes. We investigated the efficacy of resveratrol (RESV) for preventing SE-induced neurodegeneration, abnormal neurogenesis, oxidative stress and inflammation in the hippocampus. We induced SE in young rats and treated with either vehicle or RESV, commencing an hour after SE induction and continuing every hour for three-hours on SE day and twice daily thereafter for 3 days. Seizures were terminated in both groups two-hours after SE with a diazepam injection. In contrast to the vehicle-treated group, the hippocampus of animals receiving RESV during and after SE presented no loss of glutamatergic neurons in hippocampal cell layers, diminished loss of inhibitory interneurons expressing parvalbumin, somatostatin and neuropeptide Y in the dentate gyrus, reduced aberrant neurogenesis with preservation of reelin + interneurons, lowered concentration of oxidative stress byproduct malondialdehyde and pro-inflammatory cytokine tumor necrosis factor-alpha, normalized expression of oxidative stress responsive genes and diminished numbers of activated microglia. Thus, 4 days of RESV treatment after SE is efficacious for thwarting glutamatergic neuron degeneration, alleviating interneuron loss and abnormal neurogenesis, and suppressing oxidative stress and inflammation. These results have implications for restraining SE-induced chronic temporal lobe epilepsy.
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Mishra
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Shuai
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Maheedhar
authors.initials: M
authors.lastname: Kodali
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Geetha A
authors.initials: GA
authors.lastname: Shetty
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Hattiangady
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Rao
authors.affiliation: Institute for Regenerative Medicine, Texas A &M Health Science Center College of Medicine at Scott &White, Temple, Texas, USA.|Research Service, Olin E. Teague Veterans' Affairs Medical Center, Central Texas Veterans Health Care System, Temple, Texas, USA.|Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, Texas, USA.
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Shetty
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D059330:GABAergic Neurons / Q000187:drug effects / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D007395:Interneurons / Q000187:drug effects / Q000473:pathology; D008136:Longevity / Q000187:drug effects / Q000235:genetics; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000473:pathology; D009410:Nerve Degeneration / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009478:Neuropeptide Y / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D010320:Parvalbumins / Q000378:metabolism; D011916:Rats, Inbred F344; D000091042:Reelin Protein; D000077185:Resveratrol; D012640:Seizures / Q000188:drug therapy; D012697:Serine Endopeptidases / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013226:Status Epilepticus / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D010320:Parvalbumins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D013004:Somatostatin; D012697:Serine Endopeptidases; D000077185:Resveratrol