Alterações agudas dos níveis de neurotransmissores em corpo estriado de ratos jovens após estado epiléptico induzido por pilocarpina

Abstract

RESUMO -Altas doses de agonista colinérgico muscarínico, pilocarpina, produzem alterações comportamentais, convulsões e estado epiléptico em ratos. O objetivo desse estudo foi verificar as alterações nas concentrações dos neurotransmissores em corpo estriado de ratos em desenvolvimento após estado epiléptico induzido pela pilocarpina. Ratas Wistar foram tratadas com uma única dose de pilocarpina (400mg/Kg; s.c.). Controles receberam salina. A concentração dos neurotransmissores foi determinada através do HPLC, no corpo estriado de ratos que no período de observação de 1 e 24h desencadearam estado epiléptico e não sobreviveram à fase aguda do quadro convulsivo. Foi observada redução nos níveis de dopamina, serotonina, ácido dihidroxifenilacético, ácido 5-hidroxiindolacético, e aumento no ácido 4-hidroxi-3-metoxi-fenilacético. Os resultados mostraram que a ativação do sistema colinérgico pode interagir com os sistemas dopaminérgico e serotonérgico nos mecanismos referentes à fase aguda do processo convulsivo.PALAVRAS-CHAVE: dopamina, serotonina, convulsão, pilocarpina, corpo estriado.Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status Acute alterations of neurotransmitters levels in striatum of young rat after pilocarpine-induced status epilepticus epilepticus epilepticus epilepticus epilepticus ABSTRACT -High doses of the muscarinic cholinergic agonist, pilocarpine, result in behavioural changes, seizures and status epilepticus in rats. The purpose of the present work is to invetigate the striatal neurotransmissors level in young rats after status epilepticus induced by pilocarpine. Wistar rats were treated with a single dose of pilocarpine (400mg/Kg; s.c.). Controls received saline. Young animals were closed observed for behavioural changes during 1 and 24h. In these periods, the animals that developed status epilepticus and didn't survive this acute phase of seizures had the brains removed and striatal neurotransmissors level determined by HPLC. The concentration of dopamine, serotonine, dihydroxyphenylacetic acid, 5-hydroxyindolacetic acid was reduced and an increase in 4-hydroxy-3-methoxy-phenylacetic acid was observed. These results suggest that cholinergic activation can interage with dopaminergic and serotonergic systems in acute phase of the convulsive process in immature striatum.KEY WORDS: dopamine, serotonine, seizures, pilocarpine, striatum.Agonistas muscarínicos administrados em altas doses induzem a produção de convulsões motoras límbicas e estado epiléptico em ratos adultos 1,2 . O modelo de convulsão com dose alta de pilocarpina (400mg/Kg) revela o processo convulsivo através de alterações comportamentais, eletroencefalográficas e pela pres...

The Effects of Quinacrine, Proglumide, and Pentoxifylline on Seizure Activity, Cognitive Deficit, and Oxidative Stress in Rat Lithium-Pilocarpine Model of Status Epilepticus

“…Besides its definite association with seizure activity, cAMP also plays a key role in biochemical regulation of the cognitive process of memory consolidation [ 61 ]. Earlier studies have also revealed that OS-related seizures produce changes in antioxidant enzyme activities [ 6 , 8 , 13 , 14 ] and still other studies have related Pc-induced epileptic activity with the disturbance in OS activities [ 3 , 4 , 16 ]. Neuronal hyperexcitability and excessive production of free radicals have been implicated in the pathogenesis of a considerable range of neurological disorders, including epilepsy [ 62 – 64 ].…”

“…Reactive oxygen species (ROS) can dramatically affect the structure and function of neurons and recently Freitas et al [ 15 ] suggested an evidence based role of ROS in the pathophysiology of SE. Importantly, epilepsy induced by pilocarpine in rodent models can provide information regarding oxidative stress-related epileptic activity [ 3 , 4 , 16 – 18 ]. Besides epileptic seizure activities, oxidative stress has also been related with cognitive impairment [ 19 – 22 ].…”

Role of oxidative stress in epileptic seizures

“…The acute administration of high dose pilocarpine in rodents is an experimental model largely used to study the pathophysiology of seizures (de Freitas et al, 2003). The epilepsy model induced by high-dose pilocarpine has revealed behavioral and electroencephalographic alterations that are similar to those in human TLE (Turski et al, 1983).…”

Alleviation of Oxidative Damage and Involvement of Nrf2-ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

“…The frequency and severity of epileptic seizures are ameliorated and oxidative damage is attenuated in Ptx-treated SE rats [25, 26]. Clinical and experimental studies have suggested the implication of dopaminergic system in seizures [27], such as a decreased DA content in hippocampus (Hip) and striatum of SE rats [26, 28], as well as the reduced dopamine transporter (DAT) in substantia nigra (SN) and midbrain of epilepsy patients [29, 30]. Therefore, in the present study, the efficacy of intranasal Ptx delivery in epileptic seizures was investigated by analyzing the alteration of mesodopaminergic system and hippocampus in SE rats induced by lithium-pilocarpine (Li-Pc), based on the severe implication of mesodopaminergic system and Hip in SE [26, 29].…”