Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice. 2014

Ran-Ran Zhao, and Xiao-Chen Xu, and Fei Xu, and Wei-Li Zhang, and Wen-Lin Zhang, and Liang-Min Liu, and Wei-Ping Wang
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.

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.

UI MeSH Term Description Entries
D007696 Kindling, Neurologic The repeated weak excitation of brain structures, that progressively increases sensitivity to the same stimulation. Over time, this can lower the threshold required to trigger seizures. Kindlings, Neurologic,Neurologic Kindling,Neurologic Kindlings
D007859 Learning Disabilities Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These may result from organic or psychological conditions. Relatively common subtypes include DYSLEXIA, DYSCALCULIA, and DYSGRAPHIA. Adolescent Learning Disabilities,Adult Learning Disabilities,Child Learning Disabilities,Developmental Academic Disability,Developmental Academic Disorder,Developmental Disabilities of Scholastic Skills,Learning Disabilities, Adolescent,Learning Disabilities, Child,Learning Disorders,Academic Disorder, Developmental,Adult Learning Disorders,Developmental Disorders of Scholastic Skills,Learning Disorders, Adult,Learning Disturbance,Scholastic Skills Development Disorders,Academic Disabilities, Developmental,Academic Disability, Developmental,Academic Disorders, Developmental,Adolescent Learning Disability,Adult Learning Disability,Adult Learning Disorder,Child Learning Disability,Developmental Academic Disabilities,Developmental Academic Disorders,Disabilities, Adolescent Learning,Disabilities, Adult Learning,Disabilities, Child Learning,Disabilities, Developmental Academic,Disabilities, Learning,Disability, Adolescent Learning,Disability, Adult Learning,Disability, Child Learning,Disability, Developmental Academic,Disability, Learning,Disorder, Learning,Disorders, Adult Learning,Disorders, Learning,Disturbance, Learning,Disturbances, Learning,Learning Disabilities, Adult,Learning Disability,Learning Disability, Adolescent,Learning Disability, Adult,Learning Disability, Child,Learning Disorder,Learning Disorder, Adult,Learning Disturbances
D008297 Male Males
D008315 Malondialdehyde The dialdehyde of malonic acid. Malonaldehyde,Propanedial,Malonylaldehyde,Malonyldialdehyde,Sodium Malondialdehyde,Malondialdehyde, Sodium
D008569 Memory Disorders Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions. Memory Loss,Age-Related Memory Disorders,Memory Deficits,Memory Disorder, Semantic,Memory Disorder, Spatial,Memory Disorders, Age-Related,Retention Disorders, Cognitive,Semantic Memory Disorder,Spatial Memory Disorder,Age Related Memory Disorders,Age-Related Memory Disorder,Cognitive Retention Disorder,Cognitive Retention Disorders,Deficit, Memory,Deficits, Memory,Memory Deficit,Memory Disorder,Memory Disorder, Age-Related,Memory Disorders, Age Related,Memory Disorders, Semantic,Memory Disorders, Spatial,Memory Losses,Retention Disorder, Cognitive,Semantic Memory Disorders,Spatial Memory Disorders
D008687 Metformin A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289) Dimethylguanylguanidine,Dimethylbiguanidine,Glucophage,Metformin HCl,Metformin Hydrochloride,HCl, Metformin,Hydrochloride, Metformin
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D010433 Pentylenetetrazole A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GAMMA-AMINOBUTYRIC ACID antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. Leptazole,Pentamethylenetetrazole,Pentetrazole,Cardiazol,Corasol,Corazol,Corazole,Korazol,Korazole,Metrazol,Metrazole,Pentazol,Pentylenetetrazol
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D003292 Convulsants Substances that act in the brain stem or spinal cord to produce tonic or clonic convulsions, often by removing normal inhibitory tone. They were formerly used to stimulate respiration or as antidotes to barbiturate overdose. They are now most commonly used as experimental tools. Convulsant,Convulsant Effect,Convulsant Effects,Effect, Convulsant,Effects, Convulsant

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