Modulatory effects of neuropeptides on pentylenetetrazol-induced epileptic seizures and neuroinflammation in rats

SUMMARY OBJECTIVE We aimed to explore the effects of neuropeptides ghrelin, obestatin, and vasoactive intestinal peptide (VIP) on seizures and plasma concentrations of neuroinflammation biomarkers including calcitonin gene-related peptide (CGRP), substance-P (SP), and interleukin-1 beta (IL-1β) in pentylenetetrazol-induced seizures in rats. METHODS Ghrelin (80 µg/kg), obestatin (1 µg/kg), VIP (25 ng/kg) or saline were administered to rats intraperitoneally 30 min before pentylenetetrazole (PTZ, 50 mg/kg) injections. Stages of epileptic seizures were evaluated by Racine's scale, and plasma CGRP, SP, and IL-1β concentrations were measured using ELISA. RESULTS Both obestatin and VIP shortened onset-time of generalized tonic-clonic seizure, respectively, moreover VIP also shortened the onset-time of first myoclonic-jerk induced by PTZ. While PTZ increased plasma CGRP, SP and IL-1β concentrations, ghrelin reduced the increases evoked by PTZ. While VIP further increased PTZ-evoked CGRP levels, it diminished IL-1β concentrations. However, obestatin did not change CGRP, SP, and IL-1β concentrations. CONCLUSION Our results suggest that ghrelin acts as an anticonvulsant, obestatin acts as a proconvulsant, and VIP has dual action on epilepsy. Receptors of those neuropeptides may be promising targets for epilepsy treatment.

RESUMO OBJETIVO Nosso objetivo foi explorar os efeitos dos neuropeptídeos grelina, obestatina e peptídeo intestinal vasoativo (VIP) nas convulsões e concentrações plasmáticas de biomarcadores neuroinflamatórios, incluindo peptídeo relacionado ao gene da calcitonina (CGRP), substância-P (SP) e interleucina-1 beta (IL-1β) em convulsões induzidas por pentilenotetrazol em ratos. MÉTODOS Grelina (80 µg/kg), obestatina (1 µg/kg), VIP (25 ng/kg) ou solução salina foram administrados a ratos intraperitonealmente 30 minutos antes de injeções de pentilenotetrazol (PTZ, 50 mg/kg). Os estágios das crises epilépticas foram avaliados pela escala de Racine e as concentrações plasmáticas de CGRP, SP e IL-1β foram medidas usando Elisa. RESULTADOS Tanto a obestatina quanto o VIP encurtaram o tempo de início da crise tônico-clônica generalizada, respectivamente. Além disso, o VIP também encurtou o tempo de início do primeiro impulso mioclônico induzido por PTZ. Enquanto o PTZ aumentou as concentrações plasmáticas de CGRP, SP e IL-1β, a grelina reduziu os aumentos evocados por PTZ. Enquanto o VIP aumenta ainda mais os níveis de CGRP evocados por PTZ, diminui as concentrações de IL-1β. No entanto, a obestatina não alterou as concentrações de CGRP, SP e IL-1β. CONCLUSÃO Nossos resultados sugerem que a grelina tem anticonvulsivante, a obestatina tem proconvulsivante e o VIP tem ação dupla na epilepsia. Receptores desses neuropeptídeos podem ser alvos promissores para o tratamento da epilepsia.

involvement of GABA-ergic transmission in the anticonvulsant effect of ginkgo biloba against kainic acid-induced seizures in mice

Ginkgo biloba[GbE] is an herbal product that has been proven to be effective in many neurological disorders. However, its anticonvulsant activity is not sufficiently studied. The aim of this work is to study the anticonvulsant activity of GbE and the role of GABA-ergic transmission in this effect.[1] Studying the anticonvulsant activity of GbE in different dose levels [20, 30 and 50 mg/kg/d, orally] for 15 days against kainic acid [KA]-induced seizures in mice. [2] Measurement of the brain giutamate and GAB A levels and glutamate decarboxylase [GAD] activity. GbE showed a protective effect for animals against KA-induced seizures in a dose-related manner. This appeared in form of a significant increase in time of seizure onset and decrease in percent of seizures and mortality in animals treated with GbE. Furthermore, there was a significant decrease in brain glutamate level and increase in GABA level and GAD activity in GbE-treated groups relative to KA-treated group. From the obtained results, we can conclude that GbE has effective anticonvulsant activity against KA-induced seizures. This effect may be mediated via various mechanisms but GABA-ergic transmission plays a vital role in this effect. Future research directions include further studies of the other possible mechanisms of GbE involved in its anticonvulsant and neuropotective activity

Effects of misoprostrol on pentylenetetrazol-induced seirures in mice

The effects of prostaglandin E - analogue misoprostol on the susceptibility to pentilenetetrazol (PTZ) - induced seizures were examined in mice. Misoprostol (200-800 mug/kg), given subcutaneously 45 min before the subconvulsive dose of PTZ (30 mg/kg, i.p) provoked dose-dependent clonic-tonic seizures (30 to 100 percent) and mortality in mice. At 300 g/kg, s.c., misoprostol pretreatment significantly (p<0.05) lowered the onset latency to first convulsion as well as the latency to mortality induced by a convulsive dose of PTZ (60 mg/kg, i.p.). At this dose misoprostol was found to lower the CD50 and Ld50 values for PTZ by 21 percent and 36 percent respectively. The results suggest that prostaglandins are likely to lower the threshold for convulsions.

Justicia pectoralis no previne las convulciones inducidas por PTZ y PTX / Justicia pectoralis in not prevention of the comvulsions induced by PTZ and PTX

Se evaluan los efectos de extractos acuosos de Justicia pectoralis sobre las convulsiones inducidas por pentilentetrazol y picrotoxina en ratones. Se realizaron curvas dosis-efectos de estos agentes convulsivantes en ausencia y presencia de una decocción de la planta verde, de un liofilizado hidrosoluble de la planta seca y de un psicofármaco de referencia, diazepam. Se demostró que los extractos de Justicia pectoralis no protegen contra las convulsiones inducidas por los agentes convulsivantes a diferencia del diazepam. Los resultados indican que el posible efecto sedante de Justicia pectoralis no está relacionado con el mecanismo de acción de los ansiolíticos del tipo de las benzodiazepinas