title: Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure.
abstract: Epilepsy remains a major medical problem for which there is no effective treatment. Oxidative damage plays an important role in epilepsy pathogenesis and may represent a target for treatment of epilepsy. Recent studies have suggested that nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative damage and accumulation of toxic metabolites. This study evaluated the role of Nrf2-ARE signal pathway in protecting the brain from seizure-mediated damage. Wistar rats and Nrf2-deficient or control mice were chronic kindled in the amygdala. Sulforaphane (SF) was used to activate Nrf2-ARE signal pathway. The progression of kindling, the cognitive impairment and oxidative stress parameters were assessed to determine the extent of seizure-mediated brain damage. Our results indicate that activation Nrf2-ARE signal pathway with SF in hippocampus suppressed the progression of amygdala kindling, and also ameliorated the cognitive impairment and oxidative stress induced by epileptic seizure. These observations suggest that Nrf2-ARE signal pathway may represent a strategic target for epilepsy therapies.
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China; Department of Neurology, Handan First Hospital, Handan, Hebei 056002, PR China.
authors: Wei
authors: W
authors: Wang
authors: Department of Neurology, Handan First Hospital, Handan, Hebei 056002, PR China.
authors: Yanfen
authors: Y
authors: Wu
authors: Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei 050017, PR China.
authors: Guoliang
authors: G
authors: Zhang
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors: Haibo
authors: H
authors: Fang
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors: Hongchao
authors: H
authors: Wang
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors: Hongmin
authors: H
authors: Zang
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors: Tao
authors: T
authors: Xie
authors: Key Laboratory of Neurology of Hebei Province, the Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China. Electronic address: ldh_wwp_lcy@163.com.
authors: Weiping
authors: W
authors: Wang
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000503:physiopathology; D000818:Animals; D061745:Antioxidant Response Elements; D004558:Electric Stimulation; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*; D013454:Sulfoxides
chemical_list: D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D013454:Sulfoxides; C016766:sulforaphane
keywords: ADD; ARE; Epilepsy; GSH; HO-1; Heme oxygenase-1; MDA; NAD(P)H: quinone oxidoreductase-1; NQO1; Nrf2; Nrf2-ARE; Oxidative stress; SF; Sulforaphane; afterdischarge duration; antioxidant response element; heme oxygenase-1; malondialdehyde; nuclear factor erythroid 2-related factor 2; reduced glutathione; sulforaphane