Open AccessNitric oxide production in the rat brain after kainate-induced seizure
Author(s) -
Lidija Radenović,
Marina Jovanović,
Ivana Vasiljević,
Milica Ninković,
Vesna Selaković,
Z Malicević
Publication year - 2002
Publication title -
acta veterinaria
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.308
H-Index - 17
eISSN - 1820-7448
pISSN - 0567-8315
DOI - 10.2298/avb0206319r
Subject(s) - kainic acid , kainate receptor , glutamate receptor , chemistry , neurotoxicity , nitric oxide , nmda receptor , hippocampus , nitric oxide synthase , forebrain , pharmacology , medicine , endocrinology , biochemistry , central nervous system , receptor , biology , ampa receptor , toxicity , organic chemistry
We investigated the role of nitric oxide (NO) as a new neurotransmitter in the control of excitability and neurotoxicity of the hippocampus, forebrain cortex, striatum and cerebellum of the rat, as well as the possible functional interaction between NO and the glutamate system. Kainic acid is an endogenous excitotoxin acting on glutamate non-N-methyl-D-aspartate (non-NMDA) receptors, that leads to neurotoxic damage resembling the alterations observed in some neurological disorders. Stimulation of glutamate receptors induces neuronal NO release, which in turn modulates glutamate transmission. We also investigated the effects of 7-nitroindazole (7-NI), a selective neuronal nitric oxide synthase inhibitor in vivo, on nitrite concentration after kainic acid injection (0.5 mg/ml, pH 7.2) unilaterally into the CA3 region of the rat hippocampus. The accumulation of nitrite, the stable metabolite of NO, was measured by the Griess reaction at different times (5 min, 15 min, 2 h, 48 hand 7 days) following kainate injection in the ipsi- and contralateral hippocampus, forebrain cortex striatum and cerebellum homogenates. 7-NI (WOmicroM) can effectively inhibit NO synthesis in rat brain after kainate-induced intrahippocampal neurotoxicity, suppressed nitrite accumulation and attenuated neuronal damage induced by NMDA overactivity. All data showed that reduction of nitrite levels in the nervous system causes overactivity resulting from the absence of the NO-mediated modulatory action. The relatively transient nitric oxide synthase inhibitory effect of 7-NI following intracerebral injection should be taken into account when using this drug to evaluate the central effects of NO. The present results implicate neuronal NO generation in the pathogenesis of both direct and secondary excitotoxic neuronal injuries in vivo. As such they suggest that neuronal NO synthase inhibitors may be useful in the treatment of neurological diseases in which excitotoxic mechanisms play a role