Nitric oxide promotes seizure activity in kainate-treated rats

Mülsch, Alexander; Busse, Rudi; Mordvintcev, Peter I.; Vanin, Anatoly F.; Nielsen, Elsebet Ø.; Scheel-Krüger, Jørgen; Olesen, Søren P.

doi:10.1097/00001756-199411000-00029

Cited by 129 publications

(58 citation statements)

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“…In the same way, Jayakumar et al (6) have found that L-arginine, a precursor of NO, inhibited picrotoxin-induced convulsions, suggesting that NO may play a role as an endogenous anticonvulsant substance. In contrast to these reports, Mülsch et al (7) demonstrated an increase in NO formation in kainate-treated mice, but a reduction in both NO production and kainate-induced convulsions in mice pretreated with nitric oxide synthase (NOS) inhibitor. They suggested that NO has a proconvulsant role in kainateinduced convulsions.…”

Section: Discussionmentioning

confidence: 85%

The Role of Nitrergic System in Lidocaine-Induced Convulsion in the Mouse

Kurt

Bilge

Kukula

et al. 2001

Japanese Journal of Pharmacology

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ABSTRACT-The effects of N-nitro-L-arginine-methyl ester (L-NAME) a nitric oxide (NO) synthase inhibitor and L-arginine, a NO precursor, were investigated on lidocaine-induced convulsions. In the first experiment, four groups of mice received physiological saline (0.9%), L-arginine (300 mg/ kg, i.p.), L-NAME (100 mg / kg, i.p.) and diazepam (2 mg/ kg), respectively. Thirty minutes after these injections, all mice received lidocaine (50 mg/kg, i.p.). In the second experiment, four groups of mice received similar treatment in the first experiment, and 30 min after these injections, all mice received a higher dose of lidocaine (80 mg/ kg). L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg) significantly decreased the incidence of lidocaine (50 mg/kg)-induced convulsions. In contrast, the L-arginine treatment increased the incidence of lidocaine (80 mg/ kg, i.p.)-induced convulsions significantly. These results may suggest that NO is a proconvulsant mediator in lidocaine-induced convulsions.

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Section: Discussionmentioning

confidence: 85%

The Role of Nitrergic System in Lidocaine-Induced Convulsion in the Mouse

Kurt

Bilge

Kukula

et al. 2001

Japanese Journal of Pharmacology

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“…NO formation is also increased during epileptic seizures as a result of Ca 2ϩ -dependent activation of endothelial (eNOS) and neuronal (nNOS) NO synthases, as shown for kainic acid-and pentylene tetrazole-induced seizures in vivo (Mülsch et al, 1994;Kaneko et al, 2002;Gupta and Dettbarn, 2003;Kato et al, 2005), and in the low-Mg 2ϩ model of epilepsy in vitro . However, whether the increase of NO formation contributes to development and/or maintenance of epileptic activity is not yet fully understood.…”

Section: Introductionmentioning

confidence: 87%

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Kovacs¹,

Rabanus²,

Otáhal³

et al. 2009

Journal of Neuroscience

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Nitric oxide (NO) modulates synaptic transmission, and its level is elevated during epileptic activity in animal models of epilepsy. However, the role of NO for development and maintenance of epileptic activity is controversial. We studied this aspect in rat organotypic hippocampal slice cultures and acute hippocampal-entorhinal cortex slices from wild-type and neuronal NO synthase (nNOS) knock-out mice combining electrophysiological and fluorescence imaging techniques. Slice cultures contained nNOS-positive neurons and an elaborated network of nNOS-positive fibers. Lowering of extracellular Mg 2ϩ concentration led to development of epileptiform activity and increased NO formation as revealed by NO-selective probes, 4-amino-5-methylamino-2Ј,7Ј-difluorofluorescein and 1,2-diaminoanthraquinone sulfate. NO deprivation by NOS inhibitors and NO scavengers caused depression of both EPSCs and IPSCs and prevented initiation of seizure-like events (SLEs) in 75% of slice cultures and 100% of hippocampal-entorhinal cortex slices. This effect was independent of the guanylyl cyclase/cGMP pathway. Suppression of SLE initiation in acute slices from mice was achieved by both the broad-spectrum NOS inhibitor N-methyl-L-arginine acetate and the nNOS-selective inhibitor 7-nitroindazole, whereas inhibition of inducible NOS by aminoguanidine was ineffective, suggesting that nNOS activity was crucial for SLE initiation. Additional evidence was obtained from knock-out animals because SLEs developed in a significantly lower percentage of slices from nNOS Ϫ/Ϫ mice and showed different characteristics, such as prolongation of onset latency and higher variability of SLE intervals. We conclude that enhancement of synaptic transmission by NO under epileptic conditions represents a positive feedback mechanism for the initiation of seizure-like events.

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“…Also, a role for NO in certain neurodegenerative processes (Southam and Garthwaite, 1993) and memory disorders (Du and Harvey, 1996;Du et al, 2000) has been proposed. NO production is increased in kainic acid (KA)-induced seizures (Mulsch et al, 1994) and inhibition of NOS activity with 7-nitroindazole, a selective nNOS inhibitor, and N-nitro-L-arginine (L-NAME), a NOS inhibitor, decreases NO production and hippocampal damage, and attenuates seizure activity (Takei et al, 1999;Takei et al, 2001). Aminoguanidine, a selective iNOS inhibitor, protects against ischemic damage in rats by suppressing the excessive production of NO (Danielisova et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

Byun

Lee

Jeon

et al. 2009

Korean J Physiol Pharmacol

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Nitric oxide (NO) has both neuroprotective and neurotoxic effects depending on its concentration and the experimental model. W e tested the effects of NG-nitro-L-arginine methyl ester (L-NAME), a nonselective nitric oxide synthase (NOS) inhibitor, and aminoguanidine, a selective inducible NOS (iNOS) inhibitor, on kainic acid (KA)-induced seizures and hippocampal CA3 neuronal death. L-NAME (50 mg/kg, i.p.) and/or aminoguanidine (200 mg/kg, i.p.) were administered 1 h prior to the intracerebroventricular (i.c.v.) injection of KA. Pretreatment with L-NAME significantly increased KA-induced CA3 neuronal death, iNOS expression, and activation of microglia. However, pretreatment with aminoguanidine significantly suppressed both the KA-induced and L-NAME-aggravated hippocampal CA3 neuronal death with concomitant decreases in iNOS expression and microglial activation. The protective effect of aminoguanidine was maintained for up to 2 weeks. Furthermore, iNOS knockout mice (iNOS − /− ) were resistant to KA-induced neuronal death. The present study demonstrates that aminoguanidine attenuates KA-induced neuronal death, whereas L-NAME aggravates neuronal death, in the CA3 region of the hippocampus, suggesting that NOS isoforms play different roles in KA-induced excitotoxicity.

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Nitric oxide promotes seizure activity in kainate-treated rats

Cited by 129 publications

References 0 publications

The Role of Nitrergic System in Lidocaine-Induced Convulsion in the Mouse

The Role of Nitrergic System in Lidocaine-Induced Convulsion in the Mouse

Endogenous Nitric Oxide Is a Key Promoting Factor for Initiation of Seizure-Like Events in Hippocampal and Entorhinal Cortex Slices

Kainic Acid-induced Neuronal Death is Attenuated by Aminoguanidine but Aggravated by L-NAME in Mouse Hippocampus

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