Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models.

E.A. Del-Bel,N. Garcia-Cairasco,P.R. Oliveira,P.K. Mishra,P.C. Jobe,J.A.C. Oliveira

doi:10.1590/s0100-879x1997000800010

Abstract

The effect of acute (120 mg/kg) and chronic (25 mg/kg, twice a day, for 4 days) intraperitonial injection of the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG) was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ) and by sound stimulation of audiogenic seizure-resistant (R) and audiogenic seizure-susceptible (S) rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg) only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg) and protected against PTZ-induced tonic seizures (80 mg/kg). The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure.

Highlights

Epilepsy is a phenomenon causing severe and continuous seizure activity such as that present in status epilepticus, or chronic spontaneous recurrent seizures
No treatment was used to favor animal survival after status epilepticus because our main goal was to study only seizures induced by a high dose of PILO and by acute and chronic low doses of PILO
Status epilepticus was induced by PILO (100 mg/ kg) in both the acutely and chronically LNOARG-treated groups (Figure 1D), with a significant effect being observed in the acutely treated group (P

Summary

Introduction

Epilepsy is a phenomenon causing severe and continuous seizure activity such as that present in status epilepticus, or chronic spontaneous recurrent seizures. Alterations in several classic neurotransmitter systems such as the glutamatergic [1] or GABAergic [2] one have been implicated in the elicitation of epileptic seizures. Other molecules such as nitric oxide (NO) have been pointed out as potential neurotransmitters or retrograde messengers [3] linked to synaptic plasticity [4] and regulation of brain excitability, including the triggering of seizure activity [5,6]. NO is formed from L-arginine by the enzyme NO synthase (NOS) [7] and the involvement of NO in epileptic disorders has been shown in experiments with systemic injection of NOS inhibitors [5,6,8,9].

Objectives

Methods

Results

Conclusion