Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure

• Published in: Brain research Vol. 1544; pp. 54 - 61
• Main Authors: Wang, Wei, Wu, Yanfen, Zhang, Guoliang, Fang, Haibo, Wang, Hongchao, Zang, Hongmin, Xie, Tao, Wang, Weiping
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.01.2014; Elsevier
• Subjects: Amygdala - drug effects; Amygdala - physiopathology; Animals; Antioxidant Response Elements; Biological and medical sciences; Electric Stimulation; Epilepsy; Epilepsy - genetics; Epilepsy - metabolism; Epilepsy - physiopathology; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Heme oxygenase-1; Hippocampus - drug effects; Hippocampus - metabolism; Isothiocyanates - pharmacology; Maze Learning - drug effects; Medical sciences; Mice; Mice, Knockout; NAD(P)H: quinone oxidoreductase-1; Nervous system (semeiology, syndromes); Neurology; Neuroprotective Agents - pharmacology; NF-E2-Related Factor 2 - metabolism; Nrf2-ARE; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Wistar; Signal Transduction - drug effects; Sulforaphane; NQO1; ADD; afterdischarge duration; Oxidative stress; sulforaphane; Epilepsy; HO-1; heme oxygenase-1; MDA; Nrf2-ARE; SF; ARE; reduced glutathione; Nrf2; NAD(P)H: quinone oxidoreductase-1; malondialdehyde; nuclear factor erythroid 2-related factor 2; GSH; antioxidant response element; Heme oxygenase-1; Sulforaphane; NADPH:quinone reductase; Nervous system diseases; Enzyme; Heme oxygenase (decyclizing); Activation; Epilepsy provoked by; Cerebral disorder; NAD; Central nervous system disease; Oxidoreductases
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2013.12.004

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.