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)

Convulsions and encephalopathy are frequent complications of childhood shigellosis. We studied the role of nitric oxide (NO) in Shigella-related seizures in an animal model. Pretreatment of mice with Shigella dysenteriae 60R sonicate elevated serum NO levels and enhanced the convulsive response to pentylenetetrazole (PTZ), as indicated by a higher mean convulsion score and a higher number of mice responding with seizures. Treatment of the mice with S-methylisothiourea sulfate (SMT), a potent inhibitor of inducible NO synthase (NOS), prevented the elevation of serum NO levels and concomitantly reduced the enhanced response to PTZ. The mean convulsion scores were 0.7, 0.7, 1.3, and 0.8 for mice treated with saline, saline and SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.001 for 60R sonicate versus saline and P = 0.013 for 60R sonicate versus 60R sonicate with SMT). The corresponding seizure rates were 40, 44, 75, and 47% for saline, saline with SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.0004 for 60R sonicate versus saline and P = 0.005 for 60R sonicate versus 60R sonicate with SMT). In contrast, injection of N-nitro-L-arginine, a selective inhibitor of constitutive NOS, neither abolished the elevation of serum NO nor attenuated the enhancement of seizures. These findings indicate that NO, induced by S. dysenteriae 60R sonicate, is involved in enhancing the susceptibility to seizures caused by S. dysenteriae.
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PMID:Role of nitric oxide in the enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae. 1056 51

To investigate nitric oxide production in the brain of the EL mouse, an inbred mutant strain of the ddY mouse that is susceptible to convulsive seizures, we measured whole brain nitric oxide metabolites, and counted the number of nitric oxide-producing cells in the parietal cortex and striatum. Nitric oxide metabolites in the brain and serum were determined by measuring levels of nitrite plus nitrate. Nitric oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase. Levels of nitrite plus nitrate in the whole brain were significantly lower than those of the control mice, although levels of nitrite plus nitrate in the serum did not differ between groups. There were significantly fewer NADPH-diaphorase-positive cells in the parietal cortex and striatum of the EL mouse compared to the ddY controls. These results suggest that lower nitric oxide production in the brain may be related to the susceptibility of the EL mouse to convulsive seizures.
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PMID:Nitric oxide production is decreased in the brain of the seizure susceptible EL mouse. 1058 20

We investigated the role of nitric oxide (NO) and brain-derived neurotrophic factor (BDNF) in the pentylenetetrazole (PTZ)-induced kindling in rats. Seizures were induced by single administration of PTZ, which was associated with an increase in levels of NO metabolites (NOx) in the hippocampus. Pretreatment with a neuronal NO synthase inhibitor, 7-nitroindazole (7-NI), diminished the PTZ-induced increase in NOx levels without affecting the seizure intensity. Repeated administration of PTZ produced a gradual increase in the seizure intensity, leading to the development of kindling. In the kindled rats, PTZ at a dose of 40 mg/kg increased NOx levels in the hippocampus, whereas it had no effect in control animals. Cotreatment of 7-NI with PTZ blocked the development of kindling and attenuated the PTZ-induced increase in NOx levels. A significant increase in BDNF levels was observed in the hippocampus of the kindled rats, which returned to the control levels following seizures induced by PTZ. 7-NI reduced the hippocampal BDNF levels in control rats and suppressed the increase of BDNF levels in the kindled rats. Our findings suggest that NO plays a role in the development of PTZ-induced kindling and that BDNF may contribute to the NO-dependent plastic changes in neuronal excitability.
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PMID:Involvement of nitric oxide in pentylenetetrazole-induced kindling in rats. 1064 32

There are contradictory reports on whether nitric oxide (NO) is a proconvulsant or anticonvulsant. Hence a study was designed to investigate the effect of NO donor l-Arginine and NO synthesis inhibitor N omega-nitro-L-arginine (NOARG) on electroshock- and pentylenetetrazole (PTZ)-induced seizure threshold in rats. L-arginine was tested in three doses (75, 150 and 300 mg/kg), and NOARG was administered in doses of 4, 8 and 16 mg/kg. L-Arginine increased the intensity of current required to produce a threshold seizure, whereas NOARG had the opposite effect. In PTZ-induced seizures, L-arginine significantly decreased the dose of PTZ required to produce a threshold seizure, while NOARG increased it. Hence, it was concluded that NO synthase inhibition had the opposite effect in electroshock- and PTZ-induced seizures, meriting further studies on the mechanism of effect.
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PMID:Role of nitric oxide in electroshock and pentylenetetrazole seizure threshold in rats. 1066 6

The role of nitric oxide (NO) on acute hypoglycemia-induced seizures in mice was investigated using insulin as the hypoglycemic agent. The NO precursor L-arginine in the doses of 150, 500 and 750 mg/kg exhibited a dose-dependent protective effect against seizures induced by 8 mu/kg insulin. The NO synthase inhibitor (L-NMMA) at the doses of 50 and 100 mg/kg potentiated the subconvulsive doses of insulin (2 mu/kg). The onset, duration, number of seizures and the mortality were noted in a 2 hr study period. The results of this study suggest than NO plays an important protective role in acute hypoglycemia induced seizures which are known to occur through the activation of NMDA receptors.
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PMID:Role of nitric oxide on insulin induced seizures in mice. 1077 87

While seizure attack is one of the serious complications during the hyperbaric oxygen (HBO) therapy, there is still no direct evidence showing that HBO can induce neuronal damage in the brain. The objective of this study was first to investigate whether HBO would lead to neurotoxicity in the primary rat cortical culture. Second, since alterations in neurotransmitters have been suggested in the pathophysiology of central nervous system (CNS) oxygen toxicity, the protective effects of the N-methyl-D-aspartate (NMDA) receptor antagonism and nitric oxide (NO) synthase inhibition on the HBO-induced neuronal damage were examined. The results showed that HBO exposure to 6 atmosphere absolute pressure (ATA) for 30, 60, and 90 min increased the lactate dehydrogenase (LDH) activity in the culture medium in a time-dependent manner. Accordingly, the cell survival, measured by the 3,(4,5-dimethyl-2-thiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT) assay, was decreased after HBO exposure. Pretreatment with the NMDA antagonist MK-801 protected the cells against the HBO-induced damage. The protective effect was also noted in the cells pretreated with L-N(G)-nitro-arginine methyl ester, an NO synthase inhibitor. Thus, our results suggest that activation of NMDA receptors and production of NO play a role in the neurotoxicity produced by hyperbaric oxygen exposure.
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PMID:Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures. 1103 85

We evaluated age-related changes in nitric oxide (NO) production in the brains of EL mice, a strain highly susceptible to seizures. A group of EL(s) mice were tossed up weekly to induce convulsive seizures, while in a nonstimulated EL(ns) group induction of convulsive seizures was avoided. Brain levels of nitrite plus nitrate (NOx) in EL(ns) mice were significantly higher than in nonstimulated mice at 10 days, and also higher than levels at 15 and 50 weeks in either EL(s) or EL(ns) mice. A significantly higher number of NO-producing cells were demonstrated in the hippocampus and parietal cortex by staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase in EL(s) mice at the ages of 15 and 50 weeks than in EL(ns) mice at the age of 6 weeks. In EL(ns) mice, significantly fewer neurons showed NADPH-diaphorase staining in the hippocampus, striatum and parietal cortex at the age of 50 weeks than at 6 weeks. The present results suggest that whole-brain NOx levels in EL(ns) and EL(s) mice and numbers of NADPH-diaphorase-positive neurons in EL(ns) mice decreased with aging, while increasing of numbers of such neurons in EL(s) mice were assumed to develop in compensation for reduction in whole-brain NOx levels.
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PMID:Age-related alterations of nitric oxide production in the brains of seizure-susceptible EL mice. 1111 84

At variance with pilocarpine-induced epilepsy in the laboratory rat, pilocarpine administration to the tropical rodent Proechimys guyannensis (casiragua) elicited an acute seizure that did not develop in long-lasting status epilepticus and was not followed by spontaneous seizures up to 30 days, when the hippocampus was investigated in treated and control animals. Nissl staining revealed in Proechimys a highly developed hippocampus, with thick hippocampal commissures and continuity of the rostral dentate gyri at the midline. Immunohistochemistry was used to study calbindin, parvalbumin, calretinin, GABA, glutamic acid decarboxylase, and nitric oxide synthase expression. The latter was also investigated with NADPH-diaphorase histochemistry. Cell counts and densitometric evaluation with image analysis were performed. Differences, such as low calbindin immunoreactivity confined to some pyramidal cells, were found in the normal Proechimys hippocampus compared to the laboratory rat. In pilocarpine-treated casiraguas, stereological cell counts in Nissl-stained sections did not reveal significant neuronal loss in hippocampal subfields, where the examined markers exhibited instead striking changes. Calbindin was induced in pyramidal and granule cells and interneuron subsets. The number of parvalbumin- or nitric oxide synthase-containing interneurons and their staining intensity were significantly increased. Glutamic acid decarboxylase(67)-immunoreactive interneurons increased markedly in the hilus and decreased in the CA1 pyramidal layer. The number and staining intensity of calretinin-immunoreactive pyramidal cells and interneurons were significantly reduced. These findings provide the first description of the Proechimys hippocampus and reveal marked long-term variations in protein expression after an epileptic insult, which could reflect adaptive changes in functional hippocampal circuits implicated in resistance to limbic epilepsy.
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PMID:The spiny rat Proechimys guyannensis as model of resistance to epilepsy: chemical characterization of hippocampal cell populations and pilocarpine-induced changes. 1145 85

The neuronal isoform of nitric oxide synthase (nNOS), a NADPH-dependent diaphorase, is considered to play a role in motoneuron death induced by sciatic nerve transection in neonatal rats. Neuronal loss in these circumstances has been correlated with nitric oxide (NO) production and NADPH-diaphorase positivity in motoneurons after axotomy. In the present study we looked for a possible protective effect of melatonin, an antioxidant agent and inhibitor of nNOS, on spinal motoneurons after axonal injury. Neonatal Wistar rats (P2) were submitted to sciatic nerve transection and allowed to survive to P7. Melatonin at doses of 1, 5, 10, 50 and 100 mg/kg was given subcutaneously before and at intervals after the surgery. Controls operated in the same way received dilution vehicle or no treatment. The animals were killed by perfusion of fixative and the spinal cord was examined in serial paraffin sections. The motoneurons of the sciatic pool were counted in the axotomized and contralateral sides. Immunohistochemistry for nNOS and glial fibrillary acidic protein was used to evaluate nNOS expression in the axotomized cells and the astrocytic response. We found that melatonin at doses of 1-50 mg/kg decreased neuronal death. Astrocytic hypertrophy in melatonin treated animals was less intense. There were no differences in nNOS expression between treated and control rats, and surviving motoneurons of the sciatic pool did not express the enzyme, suggesting that nNOS may not be involved in neuronal death or survival in these experimental conditions. Possible mechanisms of melatonin neuroprotection, which was equally effective at doses of 1-50 mg/kg, are discussed. Doses of 50 and 100 mg/kg caused failure to thrive, seizures or death. The fact that neuroprotective doses were far smaller than toxic ones should encourage testing of melatonin in neurologic diseases.
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PMID:Neuroprotective action of melatonin on neonatal rat motoneurons after sciatic nerve transection. 1181 4

The aim of this study was to evaluate the role of nitric oxide (NO) upon hyperbaric oxygen (HBO) toxicity in male Sprague-Dawley rats during exposure to 0.5 MPa >99% O(2). In the first experiment, the selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) was injected intraperitoneally (ip) in 15 rats. Another 15 rats received vehicle injections of peanut oil intraperitoneally. Latency to observable tonic-clonic convulsions and motor activity during the HBO exposure were scored and compared between the control group and the 7-NI group. The results showed that injection of 7-NI (30 mg/kg) significantly prolonged the latency to observable tonic-clonic convulsions. The 7-NI group also showed a significant decrease in motor activity compared with the control group. A second experiment was performed to measure the effect of 7-NI injections upon open-field activity during normobaric conditions. Twenty-four male Sprague-Dawley rats were randomly divided into three groups, each consisting of eight rats receiving 30 mg/kg 7-NI injections, 10 mg/kg 7-NI injections or vehicle injections of peanut oil intraperitoneally, respectively. The results showed that injection of 7-NI led to a significant dose-dependent reduction in horizontal and vertical activities. This study shows that 7-NI prolongs the latency to hyperoxia-induced seizures. However, it also demonstrates that 7-NI in doses ranging from 30 to 10 mg/kg has a secondary effect upon motor behavior in general. It can therefore not be ruled out that the protective effect of 7-NI upon HBO intoxication is partly due to reduced motor activity.
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PMID:Behavioral effects of 7-nitroindazole on hyperbaric oxygen toxicity. 1212


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