title: Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice.
abstract: Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.
authors.affiliation: Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China; Department of Emergency, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Ran-Ran
authors.initials: RR
authors.lastname: Zhao
authors.affiliation: Department of Neurology, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Hospital of Handan, Handan, Hebei 056002, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Occupational Medicine and Enviromental Heath, Hebei Medical University School of Public Health, Shijiazhuang, Hebei 050071, PR China.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China.
authors.forename: Liang-Min
authors.initials: LM
authors.lastname: Liu
authors.affiliation: Key Laboratory of Neurology of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050071, PR China. Electronic address: wangweip2014@126.com.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000633:toxicity; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D007859:Learning Disabilities / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D000975:Antioxidants; D003292:Convulsants; D018696:Neuroprotective Agents; D008315:Malondialdehyde; D008687:Metformin; D005978:Glutathione; D010433:Pentylenetetrazole
keywords: Cognition; Epilepsy; Metformin; Morris water maze; Oxidative stress