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)

Administration of tacrine (5 mg/kg i.p.), an anticholinesterase agent, in rats pretreated (24 h beforehand) with lithium chloride (LiCl; 12 mEq/kg i.p.) enhances the expression of neuronal nitric oxide (NO) synthase (NOS), increases NO, and causes seizures and hippocampal damage. Here we report immunohistochemistry evidence showing that in rat LiCl and tacrine enhance the expression of cyclooxygenase type 2 (COX-2) enzyme protein in the dorsal hippocampus and elevate brain PGE2 content during the preconvulsive period. The latter effect, but not enhanced COX-2 expression, is inhibited by previous (30 min before tacrine) administration of N omega-nitro-L-arginine-methyl ester (L-NAME; 10 mg/kg i.p.), an inhibitor of NO synthesis, thus implicating NO in the mechanism of stimulation of COX activity leading to elevation of brain PGE2 content. Indomethacin (10 mg/kg given i.p. 30 min before tacrine), an inhibitor of COX activity, prevented brain PGE2 elevation and abolished the expression of seizures and hippocampal damage thus supporting a role for this metabolite of the arachidonic acid cascade in the mechanisms of LiCl and tacrine-evoked neurotoxicity in rat.
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PMID:Systemic administration of N omega-nitro-L-arginine methyl ester and indomethacin reduces the elevation of brain PGE2 content and prevents seizures and hippocampal damage evoked by LiCl and tacrine in rat. 950 Sep 67

The decrease in the seizure threshold for pentylenetetrazole in diazepam-withdrawn mice was not significantly affected by L-arginine (50 and 100 microg/mouse, i.c.v.), which did have an antiseizure effect in chronically vehicle-treated mice.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nitroprusside (25 and 50 microg/mouse, i.c.v.) increased the seizure threshold for pentylenetetrazole in both diazepam-withdrawn mice and chronically vehicle-treated mice.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 involvement of the L-arginine-nitric oxide (NO) pathway in the pathogenesis of hyperoxia-induced seizures was studied by using agents controlling NO levels. We selected two inhibitors of nitric oxide synthase, the systemic inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and the novel cerebral-specific inhibitor 7-nitroindazole, and two generators of NO, the NO donor S-nitroso-N-acetylpenicillamine and the physiological precursor L-arginine. Rats with chronic cortical electrodes were injected intraperitoneally with different doses of one of the agents or their vehicles before exposure to 0.5 MPa O2 and O2 with 5% CO2 at an absolute pressure of 0.5 MPa. The duration of the latent period until the onset of electrical discharges in the electroencephalogram was used as an index of central nervous system O2 toxicity. The two nitric oxide synthase inhibitors L-NAME and 7-nitroindazole significantly prolonged the latent period to the onset of seizures on exposure to both hyperbaric O2 and to the hypercapnic-hyperoxic mixture. Pretreatment with the NO donor S-nitroso-N-acetylpenicillamine significantly shortened the latent period, whereas L-arginine, the physiological precursor of NO, significantly prolonged the latent period to onset of seizures. Our results suggest that the L-arginine-NO pathway is involved in the pathophysiology of hyperoxia-induced seizures via various regulating mechanisms.
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PMID:L-arginine-NO pathway and CNS oxygen toxicity. 957 10

Adequate, high and deficient dietary levels of zinc (Zn) were compared in seizure-susceptible EL mice with respect to convulsions and to nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase-positive hippocampal neurons. Diaphorase positivity is associated with nitric oxide (NO) production. Convulsive seizures in the EL mice given the various diets did not differ over 1-4 weeks, but convulsions in EL mice given the Zn-deficient diet for 4 weeks were more effectively suppressed by injection of zonisamide (ZNS) (75 mg/kg intraperitoneally) than in mice receiving high- or adequate-Zn diet for the same period. Numbers of NADPH diaphorase-positive neurons in the CA1/CA2 region of the hippocampal formation were significantly higher in mice given the Zn-deficient diet for 4 weeks than in mice fed adequate Zn. Mice receiving the high-Zn diet for the same period had significantly fewer NADPH diaphorase-positive neurons in the subiculum than mice with adequate Zn. These results suggest that Zn deficiency inhibits convulsive seizures of EL mice, and that dietary Zn influences numbers of NO producing neurons in the hippocampal formation.
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PMID:Influence of dietary zinc on convulsive seizures and hippocampal NADPH diaphorase-positive neurons in seizure susceptible EL mouse. 957 68

The possible roles for nitric oxide produced by neurons in epileptic conditions have been investigated from two different aspects: microcirculation and delayed damage. Our aim was to determine whether the selective inhibition of neuronal (type 1) nitric oxide synthase by 7-nitroindazole, during seizures induced by systemic kainate, modifies hippocampal blood flow and oxygen supply and influences the subsequent hippocampal damage. Experiments were performed in conscious Wistar rats whose electroencephalogram was recorded. 7-Nitroindazole (25 mg/kg, i.p.) or its vehicle was injected 30 min before kainate administration (10 mg/kg, i.p.) and then twice at 1-h intervals. Kainate triggered typical limbic seizures evolving into status epilepticus, identified by uninterrupted electroencephalographic spike activity. The seizures were stopped by diazepam (5 mg/kg, i.p.) after 1 h of status epilepticus. Three types of experiments were performed in vehicle- and 7-nitroindazole-treated rats. (1) Hippocampal nitric oxide synthase activity was measured under basal conditions, at 1 h after the onset of the status epilepticus and at 24 h after its termination (n = 4-6 per group). (2) Hippocampal blood flow and tissue partial pressure of oxygen were measured simultaneously by mass spectrometry for the whole duration of the experiment, while systemic variables and body temperature were monitored (n = 6 per group). (3) Hippocampal damage was revealed by Cresyl Violet staining and evaluated with a lesion score seven days after status epilepticus (n = 12 per group). Hippocampal nitric oxide synthase activity was not significantly modified during status epilepticus or the following day in vehicle-treated rats. In contrast, it was inhibited by 57% in 7-nitroindazole-treated rats, both in basal conditions and after 1 h of status epilepticus, but was not different from its basal level 24 h later. 7-Nitroindazole significantly decreased basal hippocampal blood flow and tissue partial pressure in oxygen by 30% and 35%, respectively without affecting any systemic or thermal variable. During status epilepticus, 7-nitroindazole significantly reduced the increase in hippocampal blood flow by 70% and prevented any increase in the tissue partial pressure of oxygen. Seven days later, the hippocampal damage in the CA1 and CA3 layers was significantly less in 7-nitroindazole-treated rats than in vehicle-treated rats. These results indicate that the inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects neurons from seizure-induced toxicity despite reducing blood flow and oxygen supply to the hippocampus.
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PMID:Inhibition of neuronal (type 1) nitric oxide synthase prevents hyperaemia and hippocampal lesions resulting from kainate-induced seizures. 957 84

Glutamate release after ischemia, hypoxia and seizure activity plays an important role in stimulating adenosine production and release. We characterized the ionotropic glutamate receptor subtype that regulates adenosine levels in vivo and investigated the role of nitric oxide and free radicals in mediating N-methyl-D-aspartate (NMDA)-induced increases in adenosine levels. Rats received unilateral intrastriatal injections and were sacrificed 15 min postinjection by high-energy focused microwave irradiation (10 kW, 1.25 s). Adenosine levels were measured by high-performance liquid chromatography in ipsilateral and contralateral striata. NMDA and kainic acid dose-dependently increased levels of adenosine whereas (+/-)-alpha-amino-3-hydroxy-5-methyl-4-isoxazol proprionic acid had no effect. The NMDA- and kainic acid-induced increases were blocked by dizocilpine, and the kainic acid response was decreased by 6-cyano-7-nitroquinoxaline-2,3-dione. The effects of NMDA and kainic acid on levels of adenosine were not additive. Intrastriatal L-arginine decreased, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester, increased basal adenosine levels. Coadministration of NMDA with L-arginine or NG-nitro-L-arginine methyl ester did not significantly affect NMDA-induced increases in levels of adenosine. N-Tert-butyl-phenylnitrone, a free radical scavenger, reversed L-arginine-induced decreases and NMDA-induced increases in levels of adenosine. Together, these results indicate that NMDA-type ionotropic receptors play an important role in regulating in vivo levels of adenosine in rat striatum and that free radicals, but not nitric oxide, apparently are involved in NMDA-induced increases in levels of adenosine. Conversely, nitric oxide, but not free radicals, apparently exert tonic control over basal levels of endogenous adenosine.
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PMID:Levels of endogenous adenosine in rat striatum. I. Regulation by ionotropic glutamate receptors, nitric oxide and free radicals. 958 May 98

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

While zinc is essential for health, it has also been implicated in the neuropathology of several disease states such as Alzheimer's disease, epilepsy and cerebral ischemia. Recent studies have shown that oxidative and nitrosylative stresses can liberate zinc from metalloproteins in vitro. Thus, nitric oxide (NO.), a radical molecule which serves as a retrograde messenger, was studied for its effects on the in vivo accumulation of zinc in neurons. Three NO. -donors, sodium nitroprusside (SNP; >/=5 nmol), spermine-nitric oxide complex (SPER-NO; </=200 nmol), and 3-morpholino-sydnonimine (SIN-1; </=200 nmol) were administered into the dorsal hippocampus of rats. Brain tissue was stained by both the Timm's method, and with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ), a histochemical stain for metal ions and a selective fluorescent probe for zinc ions, respectively. A sporadic pattern of zinc accumulation within the perikarya, axons, and dendritic processes of certain pyramidal neurons, interneurons, and dentate granule cells was found 2 h after administrations of SNP and SPER-NO, but not with SIN-1. With SNP, sporadic perikaryal zinc staining of the pyramidal neurons and interneurons at strata oriens (SO), pyramidale (SP), and radiatum (SR) was consistently observed, but with SPER-NO, the granule cells of the dentate gyrus were preferentially stained. Administration of sodium ethylenediamine tetraacetic acid (NaEDTA, 10 nmol) 10 min before SNP resulted in a marked reduction of sporadic perikaryal zinc staining in the SO and SR. The more selective metal chelator, N,N,N', N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN, 10 nmol) injected 10 min before SNP abolished the staining of neuronal perikarya and surrounding neuropil. In addition, SNP, but not SPER-NO, induced convulsive activity. Groups of rats that manifested continuous wet dog shakes and/or generalized convulsions for at least 4-5 h after SNP were found to have generalized perikaryal Timm's staining of all neurons in the pyramidal cell layer of the subicular and cornu ammonis regions, similar to the staining found after seizures induced by kainic acid. However, after kainic acid-, but not SNP-induced seizures, Timm's staining of neuronal perikarya in the piriform cortex and amygdala was also observed. This is the first evidence that NO. can induce accumulation of zinc in neuronal perikarya and processes in the hippocampus in vivo. As a mechanism underlying the possible involvement of zinc in neurodegenerative disorders caused by excitotoxicity and/or oxidative stress, it is an alternative to release of synaptic vesicle zinc and uptake by damaged hippocampal neuronal perikarya.
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PMID:Nitric oxide generators produce accumulation of chelatable zinc in hippocampal neuronal perikarya. 966 98

Carbon monoxide (CO) is an endogenously produced gas sharing many properties with nitric oxide (NO), notably activating soluble guanylate cyclase and relaxing blood vessels. The brain can generate high quantities of CO from a constitutive enzyme, haem oxygenase (HO-2). To determine whether CO is involved in the regulatory mechanisms of cerebral blood flow (CBF), two conditions associated with a reproducible CBF increase were studied in rats: epileptic seizures induced by kainate, and hypercapnia. The HO inhibitor tin protoporphyrin (Sn-PP) did not modify the basal level of CBF, significantly reduced the increase in CBF during status epilepticus, and did not affect the cerebrovascular response to hypercapnia. It is concluded that CO participates in the regulation of CBF in specific conditions, notably those associated with glutamate release.
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PMID:Carbon monoxide regulates cerebral blood flow in epileptic seizures but not in hypercapnia. 969 25

N(G)-nitro-L-arginine (NNA; an inhibitor of nitric oxide synthase) in a dose of 40 mg/kg impaired the protective activity of ethosuximide against the clonic phase of pentylenetetrazol-induced seizures in mice. The ED50 value of ethosuximide was significantly increased from 108 to 158 mg/kg. NNA (40 mg/kg) was ineffective against the protective effects of diazepam, phenobarbital and valproate against pentylenetetrazol-induced seizures. NNA (40 mg/kg) did not influence the plasma levels of the antiepileptic drugs studied, so a pharmacokinetic interaction is not probable. L-Arginine (500 mg/kg) prevented the NNA-induced reduction of the anticonvulsive activity of ethosuximide. It can be concluded that nitric oxide participates in the expression of the anticonvulsive action of ethosuximide, but not that of diazepam, phenobarbital and valproate, against pentylenetetrazol-induced seizures.
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PMID:N(G)-nitro-L-arginine impairs the anticonvulsive action of ethosuximide against pentylenetetrazol. 1008 93


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