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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The convulsant action of 3-mercaptopropionic acid (3-MPA), a known inhibitor of glutamate decarboxylase activity, was studied in 7-, 12-, 18- and 25-day-old rats and in adult animals. 3-MPA elicited predominantly clonic, minimal seizures as well as generalized tonic-clonic (major) seizures at all developmental stages studied. The CD50 for major seizures did not change during development; CD50 for minimal seizures was significantly lower in 18-day-old rats than in older animals. Latency to the onset of seizures was shortest in 18-day-old rats and extremely long in 12- and, especially, in 7-day-old rats. This long latency might signify either changing molecular properties of glutamate decarboxylase during development or slow turnover of GABA at early postnatal stages. Electrocorticographic recordings demonstrated sharp EEG components in the frontal region as a first sign of 3-MPA action, and seizure patterns exhibited similar developmental changes as found with other seizure models (a decrease in duration of individual graphoelements and an increase in synchronization among various cortical regions). This indicates the primary importance of brain maturation in the expression of epileptic EEG phenomena. The correlation between EEG and motor phenomena was poor in the youngest animals and it ameliorated with age, but it never became perfectly coincidental.
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PMID:Motor and electrocorticographic epileptic activity induced by 3-mercaptopropionic acid in immature rats. 824 36

The effect of i.c.v. administration of Evans blue to sound sensitive DBA/2 mice and to genetically epilepsy-prone rats was studied. In mice, Evans blue (3.3-52 nmol) induced: hyperlocomotion, wild running, scratching, clonic muscle spasms, tonic seizure (latency 10-45 min), followed by death or recovery. The CD50 value for clonic seizures for Evans blue was 35(23-53) nmol. Pretreatment (45 min) with Evans blue (13-52 nmol, i.c.v.) dose-dependently reduced the incidence of sound-induced seizures in DBA/2 mice (ED50 value against clonic seizures = 30 [15-58] nmol, i.c.v). In rats, Evans blue (104 nmol, i.c.v.) induced electroencephalographic seizures in the hippocampus and cortex and behavioural limbic seizures with a latency of 15-20 min. A reduction in the mean score (from 5 to 2-3) for behavioural seizures was observed which lasted for 4-5 days in rats electrically-kindled daily in the hippocampal CA3 subsector. Sound-induced clonic seizures in kindled and non-kindled rats were reduced for 3-4 days after administration of Evans blue (104 nmol, i.c.v.).
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PMID:Proconvulsant and anticonvulsant effects of Evans blue dye in rodents. 834 7

Although a majority of studies suggest that inhibitors of nitric oxide synthase (NOS) are proconvulsant, a substantial minority indicate the opposite (i.e. that inhibitors of NOS are anticonvulsant). As a consequence, the role of endogenous nitric oxide (NO) in the expression of seizures is unclear. In the present series of experiments, we therefore assessed factors governing pro- and anticonvulsant effects of inhibitors of NOS. In mice receiving systemic injections of kainate or picrotoxin, we confirmed the hypothesis that the effects of inhibitors of NOS vary with the model of seizure: Whereas 7-nitroindazole (7-NI) reduced the latency and increased the severity of kainate-induced convulsions (Expt. 1), both 7-NI and N(omega)-nitro-L-arginine methyl ester (L-NAME) slightly delayed clonus following the systemic administration of picrotoxin at doses > or = 3.5 mg/kg but not at doses < or = 3.0 mg/kg (Expts. 2-5). Paradoxically, L-NAME but not 7-NI significantly reduced the CD50 of picrotoxin, which was approximately 2 mg/kg in control mice (Expt. 4), revealing inhibitor-specific interactions with the dose of the convulsant. Finally, we determined in rats that the effects of L-NAME on kainate-induced seizures vary as a function of genetic factors: L-NAME significantly potentiated kainate-induced convulsions in Sprague-Dawley rats but not in Wistar rats (Expt. 6).
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PMID:Factors determining proconvulsant and anticonvulsant effects of inhibitors of nitric oxide synthase in rodents. 879 57

The effects of pretreatment with pertussis toxin on pentylenetetrazole-, bicuculline-, aminophylline- and pilocarpine-induced seizures were investigated in mice. In animals treated intracerebroventricularly with pertussis toxin (0.5 microgram animal-1 120 h prior to testing), the CD50 (convulsive dose in 50%) values were considerably decreased in comparison with the CD50 in sham-treated animals. CD50 values of pentylenetetrazole, bicuculline, pilocarpine and aminophylline were calculated to be 39.9, 2.0, 262 and 141 mg kg-1, whereas they were calculated to be 57.7, 2.7, 324 and 230 mg kg-1 in sham-treated animals. The observations suggest that the enhanced sensitivity to a number of chemical convulsants irrespective of their mode of action possibly results from a functional suppression of inhibitory transmission at receptors coupled to pertussis toxin sensitive G proteins, rather than a direct action on G protein linked excitatory neurotransmission. Pertussis toxin significantly decreased the protective action of carbamazepine, increasing its ED50 (effective dose in 50%) from 14.8 to 20.1 mg kg-1 in a maximal electroshock convulsive test. It influenced the ED50 of neither diphenylhydantoin nor diazepam. The diminution of carbamazepine's efficacy might result from a summation effect of adenosine receptor antagonist properties of the drug and a suppression of transmission at adenosine receptors coupled to G proteins sensitive to pertussis toxin. Pertussis toxin pretreatment remained without any significant influence on the total plasma levels of carbamazepine, diphenylhydantoin and diazepam. This may lead to the conclusion that the interaction between pertussis toxin and carbamazepine does not seem to be of a pharmacokinetic nature and occurs probably at neuronal level.
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PMID:Intracerebroventricular pertussis toxin enhances sensitivity to chemical convulsants and decreases the protective efficacy of carbamazepine in mice. 888 Aug 93

The effect of the nitric oxide synthase (NOS) inhibitors N-nitro-L-arginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) on seizures induced by N-methyl-D-aspartate (NMDA), pilocarpine (PIL) and pentylenetetrazol (PTZ), as well as on the electroconvulsive threshold was studied in mice. It was found that L-NAME and 7-NI decreased the dose of NMDA necessary to produce clonic convulsions in 50% of animals (CD50). Such a proconvulsant effect was not observed in mice pretreated with N-nitro-D-arginine methyl ester (D-NAME), an inactive isomer of L-NAME. Neither L-NAME nor 7-NI affected the convulsions induced by PIL (clonic seizures) or PTZ (clonic and tonic seizures), having no effect on their CD50 values. Similarly, neither NOS inhibitor affected the electroshock threshold. These results, together with some literature data, indicate that nitric oxide (NO) may be regarded as an anticonvulsant substance in relation to seizures induced by NMDA and other excitatory amino acids, but not by other agents, in mice.
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PMID:The role of nitric oxide in chemically- and electrically-induced seizures in mice. 891 93

Nitric oxide may be involved in seizure phenomena even though data often seem to be contradictory. This prompted us to study the influence of nitric oxide upon electrically and chemically induced seizures. The effects of nitric oxide synthase inhibitor, NG-nitro-L-arginine (NNA), on pentylenetetrazol-, aminooxyacetic acid-, aminophylline-induced seizures or electroconvulsive shock were evaluated. NNA was applied at 1, 10 and 40 mg/ kg 0.5 and 2.0 h before chemical seizures and at 1 and 40 mg/kg 0.5 and 2.0 h prior to electroconvulsions. The nitric oxide synthase inhibitor (up to 40 mg/ kg) did not affect the susceptibility of mice to pentylenetetrazol, amino-oxyacetic acid or electroconvulsions. However, NNA significantly enhanced the convulsive properties of aminophylline when applied at 40 mg/kg, 0.5 h before the test. The CD50 value for aminophylline-induced clonus and tonus/ mortality was decreased from 233 to 191 and from 242 to 212 mg/kg, respectively. However, this pretreatment also led to a significant increase in the plasma levels of theophylline. Our results suggest that differential effects of NNA on chemically-induced convulsions might in some cases be associated with a pharmacokinetic interaction.
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PMID:NG-nitro-L-arginine, a nitric oxide synthase inhibitor, and seizure susceptibility in four seizure models in mice. 901 1

We investigated the influence of NG-nitro-L-arginine (NNA), the inhibitor of nitric oxide synthese, on seizures induced by 4-aminopyridine (4-AP), the K+ channel antagonist, in mice NNA (5, 10 and 40 mg/kg, i.p.) significantly reduced the respectives CD50 of 4-AP from 9.0 to 7.6, 7.5 and 6.8 for clonic seizures, and from 9.2 to 7.7, 7.5 and 6.9 for tonic seizures and death. Lower doses of NNA (1.0 and 2.5 mg/kg) had no effect on 4-AP-induced convulsions and lethality. Our results indicate that 4-AP-induced seizures may be, at least in part, dependent on nitric oxide level.
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PMID:NG-nitro-L-arginine sensitizes mice to 4-aminopyridine-induced seizures. 932 35

The convulsive, pro-convulsive and lethal effects of two theophylline-containing bronchodilating agents, aminophylline and acepifylline, have been evaluated in rats. Aminophylline (theophylline ethylenediamine) caused seizures and death in a dose-dependent manner; an intraperitoneal dose of 250 mg kg-1 caused seizures and death in all rats. Intraperitoneal doses of acepifylline (theophylline ethanoate of piperazine) up to 1000 mg kg-1, however, did not cause seizure or death. Further, pre-treatment of the rats by intraperitoneal administration of a subconvulsive dose (100 mg kg-1) of aminophylline caused a significant decrease in CD50 and LD50 values for pentylenetetrazole and a significant increase in the number of positive responders (i.e. rats with a pentylenetetrazole-induced seizure score of 3 or more on a seizure scale ranging from 0 to 6) and death rate compared with those obtained for rats pre-treated with an equivalent intraperitoneal dose (140 mg kg-1) of acepifylline ('equivalent dose' referred to here denotes the theophylline content of the two preparations). The study has established the neurosafety profile of acepifylline and documents a safer alternative to aminophylline for use in asthmatics suffering from concomitant epilepsy or other seizure-prone neurological defects.
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PMID:A comparative study of aminophylline- and acepifylline-induced seizures and death in the chemoconvulsion model in rats. 937 62

The effects of some neurosteroids on N-methyl-D-aspartic acid (NMDA)-induced seizures were examined in mice. Intraperitoneal (i.p.) administration of 5 alpha-pregnan-3 alpha-ol-20-one (5, 10 and 20 mg/kg). 5 beta-pregnan-3 alpha-ol-20-one (10 and 20 mg/kg), 5 alpha-pregnan-3 alpha-ol-11,20-dione (15 mg/kg), 5 alpha-androstan-3 alpha-ol-17-one (10 mg/kg) and dehydroepiandrosterone sulfate (25 mg/kg) significantly increased the dose of NMDA necessary to induce clonic convulsions in 50% of the tested animals (CD50). Furthermore, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 alpha-pregnan-3 alpha-ol-11,20-dione and 5 alpha-androstan-3 alpha-ol-17-one also protected the mice against NMDA-induced mortality. Importantly, it is only at the highest doses that neurosteroids impair motor performance of the animals, as estimated by a rotorod equilibrium procedure. The other neurosteroids tested, such as 5 alpha-pregnan-3 beta-ol-20-one (5-20 mg/kg), 5 alpha-pregnan-3 alpha,21-diol-20-one (10 and 15 mg/kg), 5 alpha-pregnan-3,20-dione (15 mg/kg) and pregnenolone sulfate (12.5-100 mg/kg) had no significant effects on the measured parameters. In another set of experiments, we evaluated the effects of neurosteroids on D-[3H]-aspartate release from rat hippocampal slices. None of the neurosteroids tested exerted a significant effect on basal D-[3H]-aspartate release. On the other hand, K(+)-stimulated D-[3H]-aspartate release was significantly attenuated by 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, alphaxalone, pregnenolone sulfate and dehydroepiandrosterone sulfate. The effect of 5 alpha-pregnan-3 alpha-ol-20-one was the most potent and was distinctly concentration-dependent, whereas the other compounds were effective only at the highest concentrations used. The above results indicate that some neurosteroids administered in non-sedative doses can protect mice against NMDA-induced seizures and mortality; furthermore, they inhibit D-[3H]-aspartate release in rat hippocampal slices.
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PMID:Protective effects of neurosteroids against NMDA-induced seizures and lethality in mice. 945 34

In the present study we examined effects of some neurosteroids on the kainate-induced seizures, lethality and neurotoxicity in mice. We found that 5 alpha-pregnan-3 alpha-ol-20-one (allopregnanolone; 10 and 20 mg/kg) markedly elevated CD50 for kainate-induced convulsions, whereas 5 beta-pregnan-3 alpha-ol-20-one, 5 alpha-pregnan-3 alpha-ol-11,20-dione, 5 alpha-androstan-3 alpha-ol-17-one, dehydroepiandrosterone sulfate, pregnenolone sulfate and aminosteroid (U-107) were ineffective in that test. Furthermore, 5 alpha-pregnan-3 alpha-ol-20-one (5-20 mg/kg), 5 beta-pregnan-3 alpha-ol-20-one (20 mg/kg) and 5 alpha-androstan-3 alpha-ol 17-one (10 and 20 mg/kg) decreased, while dehydroepiandrosterone sulfate (25 and 50 mg/kg) and pregnenolone sulfate (25 mg/kg) elevated the kainate-induced lethality in mice. A histological analysis showed that kainate caused a dose-dependent neuronal loss of CA1 and CA3 hippocampal fields. Of the neurosteroids tested, only allopregnanolone attenuated the kainate-induced neurotoxicity. The above data indicate that neurosteroids exert moderate effects on seizures and neurotoxic effects of kainate. On the other hand, neurosteroids with a GABAA receptor agonistic or antagonistic activity decrease or increase, respectively, the kainate-evoked lethality.
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PMID:Effects of neurosteroids on kainate-induced seizures, neurotoxicity and lethality in mice. 956 44


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