Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a previous study, we reported that the sustained increase in CBF concomitant with seizures induced by kainate is mainly due to the potent vasodilator nitric oxide (NO). However, the production site of NO acting at cerebral vessels was undetermined. In the present study, we investigated whether NO responsible for the cerebral vasodilation is of either neuronal or endothelial origin. We used a putative selective inhibitor of neuronal NO synthase, 7-nitro indazole (7-NI). CBF was measured continuously in parietal cortex by means of laser Doppler flowmetry in awake rats. Systemic variables and electroencephalograms were monitored. Kainate (10 mg/kg i.p.) was given to rats previously treated with saline (n = 8) or 7-NI (25 mg/kg i.p., n = 8) or L-arginine (300 mg/kg i.p., n = 8) followed 30 min later by 7-NI (25 mg/kg i.p.). Under basal conditions, 7-NI decreased CBF by 27% without modifying the mean arterial blood pressure. Under kainate, 7-NI prevented significant increases in CBF throughout the seizures despite sustained paroxysmal electrical activity. L-arginine, the substrate in the production of NO, prevented any decrease in CBF under 7-NI in basal conditions and partially, but nonsignificantly, reversed the cerebrovascular influence of 7-NI during seizures. In a separate group of rats (n = 6), inhibition of cortical NO synthase activity by 7-NI was assayed at 73%. The present results show that neurons are the source of NO responsible for the cerebrovascular response to seizure activity after kainate systemic injection.
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PMID:Nitric oxide of neuronal origin is involved in cerebral blood flow increase during seizures induced by kainate. 897 91

Endothelin (ET) is a potent vasoconstrictor which has also been proposed to act as a neuromodulator. We have investigated the action of ET-1 on neurones in vivo, using c-fos as a marker of neuronal activation. Intrastriatal injection of ET-1 caused seizures and barrel rolling which were prevented by pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and attenuated by the nitric-oxide synthase inhibitor N omega-nitro-L-arginine (L-NNA). In association with these behaviours, a dramatic increase in c-fos mRNA expression was seen in the cerebral cortex. This increase was blocked by both MK-801 and L-NNA. We suggest that ET-1 modulates the activity of cortical afferents to the striatum, and causes seizures via an NMDA receptor-dependent mechanism.
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PMID:Cortical induction of c-fos by intrastriatal endothelin-1 is mediated via NMDA receptors. 905 83

Nitric oxide (NO) formation has been shown in many neuronal tissues subserves a variety of functions. N-Methyl-D-aspartate (NMDA) receptor stimulation which releases nitric oxide and raises cGMP levels, mediates epileptiform activity induced by various agents. Disinhibition of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and/or activation of NMDA receptor appears to be factors involved in the initiation and generalization of the pentylenetetrazole (PTZ) induced seizures. In the present study, we examined the effects of N(omega)-nitro-L-arginine methylester (L-NAME) which inhibits nitric oxide synthase, on PTZ and strychnine induced seizures in mice. L-NAME (100 mg/kg) significantly prolonged the onset time of tonic generalized extension without affecting myoclonic jerks and tonic-clonic convulsions. L-NAME (200 mg/kg) significantly delayed three characteristic behavioral changes including first myoclonic jerk (FMJ), generalized clonic seizure (GCS) and tonic generalized extension (TGE). The effects of L-NAME were reversed by L-arginine (1000 mg/kg). L-NAME (100 and 200 mg/kg) significantly delayed the onset time of strychnine induced TGE. The effects of both doses of L-NAME were reversed by L-arginine. In conclusion, our results demonstrate that NO synthase inhibition suppresses the onset time of PTZ and strychnine induced seizures. Under the light of our current knowledge NO synthase inhibitors seem far away to be considered as a group of antiepileptic drugs. On the other hand there are some strong evidences about the role of NO in central pathophysiological mechanisms.
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PMID:L-NAME inhibits pentylenetetrazole and strychnine-induced seizures in mice. 912 36

The ability of three nitric oxide (NO) donor compounds to modify ligand binding to kainate receptors was studied in tissue from human adult autopsy brains. Binding of [3H]kainic acid (5 nM) was measured in frontal cortex membranes made from Brodmann area 8 (BA 8) and autoradiographically using sections of frontal cortex (BA 8 and 9). None of the three donors, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), S-nitrosocysteine (Cys-NO) and 3-morpholinosydnonimine chloride (SIN-1) altered the specific binding of [3H]kainic acid. Nitrite accumulation assays confirmed that adequate amounts of NO were released by the donors under the ligand binding conditions used. The findings show that binding to the kainate receptor, in contrast to the other ionotropic glutamate receptors, is not affected by NO and strongly suggest that endogenous NO produced by NO synthase (NOS) does not modulate kainate receptors in vivo. Mechanisms whereby NOS inhibitors potentiate kainic acid-induced seizures in animal models may include altered modulation of glutamate N-methyl-D-aspartate (NMDA) receptors.
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PMID:Nitric oxide does not modulate kainate receptor binding in human brain. 935 Aug 50

The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 microg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice. Sodium nitroprusside (25 and 50 microg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice. In addition, the antiseizure effect of L-arginine was blocked by the nitric oxide (NO) synthase inhibitor, N-nitro-L-arginine (NOARG) and the NO scavenger, hemoglobin, while the effect of sodium nitroprusside was inhibited by hemoglobin, but not by NOARG, indicating that the antiseizure effect of L-arginine, but not that of sodium nitroprusside, is mediated by NO production resulting from the activation of NO synthase. Therefore, a decrease in the NO production via NO synthase may be involved in the hypersusceptibility to pentylenetetrazole during diazepam withdrawal.
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PMID:Role of nitric oxide in the hypersusceptibility to pentylenetetrazole-induced seizure in diazepam-withdrawn mice. 957 Apr 43

The role of nitric oxide (NO) on the age-dependent selective vulnerability to the consequences of epileptic seizures was studied in 10-day old (P10) and 21-day old (P21) rats. At P10, the NO synthase (NOS) inhibitor, NG-nitro-l-arginine (LNA), increased severity of seizures while l-arginine (l-Arg), the NOS substrate, had no effect. At P21, l-Arg improved the outcome of seizures while LNA had no effect. These results demonstrated the age-dependent role of NO in epilepsy.
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PMID:Age-dependent regulation of seizure activity by nitric oxide in the developing rat. 959 65

The role of nitric oxide (NO) in the pathogenesis of viral encephalitis was investigated by using an experimental model of herpes simplex virus type 1 (HSV-1) encephalitis in Lewis rats. The expression of inducible NO synthase (iNOS) mRNA determined by Northern blotting was observed first in the olfactory bulb and the brain stem on day 5 after intranasal inoculation of HSV-1, and thereafter iNOS mRNA was detected in other brain regions, i.e., cerebrum and cerebellum. In various parts of the brain, excessive NO production was identified by electron spin resonance spectroscopy. The temporal and spatial patterns of iNOS expression coincided with those of viral propagation, as demonstrated by polymerase chain reaction for HSV-1 gene expression as well as by the plaque-forming assay. Immunohistochemical study determined that iNOS was localized mainly in monocyte-derived macrophages. Treatment of virus-infected animals with the NOS inhibitor Nomega-monomethyl-l-arginine (l-NMMA), but not Nomega-monomethyl-d-arginine, significantly ameliorated not only clinical symptoms such as paralysis and seizures but also mortality. Virus yield from brain tissue was not affected by l-NMMA treatment. It is of interest that increased expression of the antioxidant enzyme heme oxygenase-1 was observed in the HSV-1-infected brain; this increased expression was strongly inhibited by l-NMMA treatment. These data suggest that the high level of NO produced by iNOS is a pathogenic factor in HSV-1-induced encephalitis in rats.
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PMID:Role of nitric oxide in pathogenesis of herpes simplex virus encephalitis in rats. 1019 Nov 85

The distribution and time course of changes of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) positivity were studied in immature rats (12 and 25 days old) surviving motor status epilepticus (SE) induced by a high dose of pilocarpine. Motor SE characterized by continuous convulsions was interrupted after 2 h by an injection of clonazepam (0.5 mg/kg or 1 mg/kg in 12- and 25-day-old rats, respectively) in order to reduce mortality. Correlation between electroencephalographic and behavioral seizure activity was confirmed using animals with electrodes implanted bilaterally in the hippocampus and sensorimotor cortex. Brains were examined 2, 6, 13, and 21 days after motor SE using NADPH-diaphorase histochemistry. Two types of changes were found in both age groups: (a) decrease of NADPH-d positivity occurred in both neuropil and cell bodies in piriform, periamygdalar, and entorhinal cortices; and (b) NADPH-d positivity was induced in the cell bodies in the hippocampal fields CA1/2, CA3, and dentate gyrus. These changes were more intense in animals surviving SE at postnatal day 25 than in younger age group, and they peaked 2 days after SE. The changes observed after SE disappeared quickly in 12-day-old rat pups, where only moderate changes could be observed in piriform, periamygdalar, and entorhinal cortices 6 days after SE, whereas the changes in the histochemical positivity persisted in older animals even 21 days after SE.
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PMID:Changes in NADPH-diaphorase positivity induced by status epilepticus in allocortical structures of the immature rat brain. 1021 Jan 66

After transient cerebral ischemia in fetal sheep, delayed disruptions in cerebral energetics are represented by a delayed increase in cortical impedance, a progressive decrease in the concentration of oxidized cytochrome oxidase as measured by near-infrared spectroscopy, and cortical seizures. Because the production of nitric oxide (NO), a potent mediator of neuronal death, is increased during this phase, the present study investigated whether inhibition of NO synthesis could ameliorate the delayed disruption in cerebral energetics. Eleven late gestation fetal sheep were subjected to 30 min of transient cerebral ischemia in utero. Two hours later, the treatment group (n = 5) received a continuous infusion of N(G)-nitro-L-arginine, a competitive inhibitor of NO synthase, whereas the control group (n = 6) received PBS. Changes in concentration of oxidized cytochrome oxidase, cortical impedance, and electrocortical activity were observed for 3 d. A delayed increase in cortical impedance of similar magnitude and duration commenced at 14+/-4 h in the control and at 15+/-3 h in the treatment groups. The progressive decrease in oxidized cytochrome oxidase signal, by -2.2+/-0.2 micromol/L in the control and -2.0+/-0.4 micromol/L in the treatment group at 72 h postischemia, was similar in both groups. In both groups, delayed cortical seizures were indicated by intense low-frequency electrocortical activity. In the treatment group, duration of cortical seizures was increased and the intensity of the final electrocortical activity was more depressed (-19+/-1 dB versus -10+/-2 dB). The results indicate that after cerebral ischemia in fetal sheep, NO synthase inhibition does not ameliorate the delayed disruptions in cerebral energetics. However, the effect of NO synthase inhibition on delayed cortical seizures may improve our understanding of the role of NO during this phase.
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PMID:Nitric oxide synthase inhibition and delayed cerebral injury after severe cerebral ischemia in fetal sheep. 1040 Jan 27

The glutamate extracellular concentration is controlled by metabolic and neuronal pathways via release and uptake mechanisms. Stimulation of glutamate receptors induces neuronal nitric oxide (NO) release, which in turn modulates glutamate transmission. In this study, the influence of neuronally derived NO on hippocampal glutamate extracellular concentration was investigated in conditions of intense metabolic activation, i.e., during status epilepticus induced by systemic kainic acid (KA). Glutamate, arginine and citrulline concentrations were measured by microdialysis coupled to HPLC. Experiments were performed in conscious rats implanted with a microdialysis probe within the hippocampal CA3 area. Three groups were used: (1) rats treated with KA i.p. (12 mg/kg) and vehicle locally, via the microdialysis probe (n = 9); (2) rats given KA i.p. and a selective inhibitor of neuronal NO synthase, 7-nitroindazole (7-NI, 1.25 mM) locally (n = 13); (3) rats treated with saline i.p. and 7-NI locally (n = 7). Infusion of 7-NI or vehicle was performed throughout the second hour of status epilepticus. In groups 1 and 3, no significant modifications of extracellular glutamate, arginine and citrulline concentrations were measured. In group 2, the local application of 7-NI in the hippocampus during status epilepticus significantly increased extracellular glutamate and arginine concentrations, whereas citrulline concentration remained constant. The concomitant increases of extracellular glutamate and arginine concentrations under local 7-NI perfusion in seizure conditions, suggest that glutamate and arginine are linked in a common metabolic pathway and/or that glutamate is involved in the cross-talk between glia and neurons. A cerebrovascular effect of 7-NI which triggers glutamate release may also occur.
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PMID:7-Nitroindazole, a selective inhibitor of nNOS, increases hippocampal extracellular glutamate concentration in status epilepticus induced by kainic acid in rats. 1051 54


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