title: High dosage of agmatine alleviates pentylenetetrazole-induced chronic seizures in rats possibly by exerting an anticonvulsive effect.
abstract: The aim of the present study was to investigate the mechanism underlying the effects of different doses of agmatine in rats with chronic epilepsy. To generate chronic epilepsy models, rats pretreated with different doses of agmatine (20, 40 and 80 mg/kg) were intraperitoneally injected with pentylenetetrazole (35 mg/kg) for 28 consecutive days. Epileptic behavior was observed using behavioral measurements of convulsion for 1 h after each treatment with pentylenetetrazole. Morphological alterations of the hippocampal neurons were also observed using hematoxylin and eosin staining. In addition, the expression levels of glial fibrillary acidic protein and inducible nitric oxide synthase (iNOS) in the hippocampus were detected by immunohistochemistry. Furthermore, reverse transcription polymerase chain reaction was performed to detect the mRNA expression of two subunits (NR1 and NR2B) of the N-methyl-D-aspartic acid (NMDA) receptor in the rat hippocampus. The results demonstrated that administration of agmatine (80 mg/kg) significantly decreased the daily average grade of epileptic seizures and also reduced neuronal loss and astrocyte hyperplasia in the hippocampal area. Furthermore, agmatine (80 mg/kg) affected the mRNA expression levels of the NR1 subunit of the NMDA receptor, however, agmatine had no effect on the expression of iNOS in the hippocampus. Higher doses of agmatine inhibited the effect of pentylenetetrazole in rats, reduced astrocytic hyperplasia and neuronal damage in the hippocampus caused by seizures and selectively reduced the expression of the NR1 subunit of NMDA. Our results suggest that agmatine has an anticonvulsive effect in chronic epilepsy.
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Neurology, Chenzhou No. 1 People's Hospital, Chenzhou, Hunan 423000, P.R. China.
authors.forename: Fuyong
authors.initials: F
authors.lastname: Ou
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Mangdula
authors.initials: M
authors.lastname: Naren
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Dongpei
authors.initials: D
authors.lastname: Tu
authors.affiliation: Department of Neurology, The First Affiliated Hospital and Research Institute of Experimental Neurobiology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Rongyuan
authors.initials: R
authors.lastname: Zheng
keywords: N-methyl-D-aspartic acid receptor; agmatine; chronic seizures; pentylenetetrazole