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.
Highlights
Agmatine is an endogenous amine synthesized via the decarboxylation of L‐arginine mediated by arginine decarboxylase
It was demonstrated that consecutive administration of agmatine provided protection against pentylenetetrazole‐induced chronic seizures in rats
These results are consistent with previous studies that demonstrated the inhibitory effect of agmatine in acute seizure animal models [2,3]
Summary
Agmatine is an endogenous amine synthesized via the decarboxylation of L‐arginine mediated by arginine decarboxylase. Agmatine is expressed in a variety of animal organs, the brain, where it acts as a novel neurotransmitter or neuromodulator [1]. The specific physiological actions of agmatine have yet to be elucidated, numerous studies have confirmed that agmatine significantly inhibits seizures induced by maximal electroshock and pentylenetetrazole in rat models [2,3,4,5,6]. The majority of previous studies have investigated the effect of agmatine on acute seizures, and only a few studies have used chronic epilepsy animal models, which are similar to the pathological physiology of clinical epileptic patients. It was hypothesized that agmatine may have an anticonvulsive effect in chronic epilepsy. In the present study, pentylenetetrazole‐induced chronic epilepsy rat models were employed in order to examine the anticonvulsive effects of agmatine
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