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)

beta-Kainic acid, and the glycine and amino-methylphosphonate derivatives of alpha- and beta-kainic acid, have been injected intracerebroventricularly in DBA/2 mice, that show sound-induced seizure responses. An anticonvulsant effect is observed with marked protection against the tonic and clonic phases of the seizure response. ED50 values against clonus are (in mumol): beta-kainic acid, 0.09; beta-kainylglycine, 0.11; alpha-kainylglycine, 0.28; alpha-kainylaminomethylphosphonate, 0.31; beta-kainylaminomethylphosphonate, greater than 1.5. In addition a direct convulsant effect occurs after the alpha-kainyl derivatives.
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PMID:Kainic acid derivatives with anticonvulsant activity. 652 64

Focal seizure discharges were induced in the ventral aspect of the medial entorhinal cortex of awake, freely moving rats, either with cannula injections of penicillin or picrotoxin (0.02 microliters every 10-15 min) or by repetitive tetanic electrical stimulation. [14C]Deoxyglucose autoradiography (DG) was performed when animals were in a 'steady-state' with respect to electrographic discharges and/or behavioral changes. During simple interictal spikes behavior remained normal and DG labeling was increased only in the entorhinal focus and stratum moleculare of the ventral dentate gyrus. With complex spikes and short seizures animals exhibited staring, decreased responsiveness, and occasional wet dog shakes. DG labeling was increased in all layers of the dentate gyrus, Ammon's horn (ipsilateral greater than contralateral) and, to a lesser degree, in ipsilateral amygdala, and the accumbens-ventral pallidum area. During strong seizures, rearing and forelimb clonus occurred and metabolism was strongly activated bilaterally in the hippocampal formation, amygdala, accumbens, substantia nigra, and the anterior and periventricular thalamic nuclei. These studies indicate that the dentate gyrus initially restricts the entry of seizures from entorhinal cortex into the rest of hippocampus. As this is overcome there is rapid bilateral spread through the hippocampal formation with passive interruption of normal behavior. With prolonged seizure discharges there is further capture of amygdala and subcortical extrapyramidal and thalamic nuclei associated with behavioral convulsions.
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PMID:Functional anatomy of limbic seizures: focal discharges from medial entorhinal cortex in rat. 665 78

The goal of this study was to test the hypothesis that phentolamine and propranolol premedication would affect tonus differently than clonus in pentylenetetrazol (PTZ)-induced tonic-clonic seizures in dogs. Tonic-clonic seizures were induced with IV infusion of PTZ, given as an initial 300-mg bolus and then 100-mg boluses every 10 S until a seizure began. Premedication with phentolamine (2 mg/kg of body weight) significantly shortened clonus (P less than 0.05), whereas propranolol (1 mg/kg) significantly lengthened clonus (P less than 0.05). Neither phentolamine nor propranolol significantly altered the length of tonus or the dose of PTZ required to induce seizures (P greater than 0.05). This indicates that tonus and clonus may have different neural mechanisms and that adrenergic receptors may be involved in the neural mechanisms of clonus.
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PMID:Influence of phentolamine and propranolol on the length of tonus and clonus in pentylenetetrazol-induced seizures in dogs. 673 88

Audiogenic seizure-prone mice (DBA/2J) were exposed to a broad band noise source. A reproducible response consisting of wild run, clonus, and tonic stages resulted in all mice. Layers 1 and pyramidal from the parietal cortex and the molecular and Purkinje cell-rich layers from the cerebellar vermis were separately analyzed for glucose, glycogen, ATP, and phosphocreatine. Results showed a biphasic cerebellar response, with decreases in high energy phosphates occurring during the wild run and tonic stage. In the cortex, similar changes occurred in the pyramidal cell layer, but the decreases were not as pronounced as those in the cerebellum. Cells from layer 1 of the parietal cortex were not affected as much as those of the pyramidal layer, suggesting a differential effect between neuronal and nonneuronal cell populations. The greater response of the cerebellum could indicate an attempt to reduce the severity of both the wild run and the tonic extension seizure.
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PMID:Audiogenic seizure-induced changes in energy metabolites in cerebral cortical and cerebellar layers. 681

Male Long-Evans rats were stereotaxically implanted bilaterally with bipolar electrodes in the central amygdala. Rats were then kindled once daily for 1 sec until 3 consecutive Stage V [25] kindled seizures were elicited. On the following day, animals were injected (IP) with either saline, naloxone (10 mg/kg), naltrexone (10mg/kg) or morphine sulfate (10 mg/kg) and again stimulated at the kindling stimulation parameters. Saline injected animals continued to show long bilateral AD's and behaviors (i.e., forelimb clonus, rearing, falling) typical of Stage V kindled animals. In contrast, rats injected with naloxone or naltrexone showed reduced behavioral seizures. Potentiation of post-ictal spiking by morphine in amygdaloid-kindled rats was also observed supporting previous reports [7,21]. In a second experiment, the reduction of kindled seizure serverity by naloxone was systematically replicated. It is concluded that opiates can significantly modify amygdaloid-kindled seizures, and that brain endorphins may play a role in the development or maintenance of an amygdaloid-kindled seizure focus.
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PMID:Opiate modification of amygdaloid-kindled seizures in rats. 708 32

Pentylenetetrazol (PTZ) is often used in experimental models of epilepsy. The relationship of the PTZ-induced seizure sequence of myoclonus, clonus and hindlimb extension (TE) to brain PTZ levels has not been reported. This study examined this relationship and determined how different routes of PTZ administration affected brain PTZ uptake and seizure development. The critical brain PTZ level for onset of clonus ranged from 20 to 50 microg/g. Brain PTZ uptake was rapid after I.P. injection of PTZ convulsant dose (CD55) for clonus/and clonus onset occured at 4.0+/- 1.6 min. uptake was slower after S.C. administration; clonus onset occurred at 9.9 +/- 3.7 min. at a CD for TE (CD40), clonus onset occured at 5.1 +/- 3.0 and 2.4 +/- 2.4 min for S.C. and I.P. routes of administration, respectively. TE onset did not appear to depend solely on brain PTZ levels were falling . Factors that could modulate the appearance of TE are discussed.
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PMID:Relationship between pentylenetetrazol-induced seizures and brain pentylenetetrazol levels in mice. 740 Sep 61

The anticonvulsant activity of felbamate against sound-induced seizures was studied in the DBA/2 mouse model. Felbamate (10-300 mg/kg, i.p.) produced dose-dependent effects with ED50 values for the suppression of tonic, clonic and wild running phases of 23.1, 48.8 and 114.6 mg/kg, respectively. Felbamate also protected DBA/2 mice from N-methyl-D-aspartate (NMDA)-induced seizures with ED50 values of 12.1 and 29 mg/kg for tonus and clonus, respectively. Pretreatment with glycine, an agonist to the glycine/NMDA receptors, shifted the dose-response effect of felbamate to the right (ED50 = 56.8 against tonus and 94.8 mg/kg versus clonus). Similarly, D-serine, an agonist at the glycine site, shifted the ED50 of felbamate against the tonic component of audiogenic seizures from 23.1 to 78.1, and that against clonus from 48.8 to 90.3 mg/kg. Felbamate was also potent to prevent seizures induced by administration of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), an AMPA/kainate receptor agonist (ED50 = 11.8 and 20.9 mg/kg, against tonus and clonus, respectively). The data indicate that felbamate is an effective anticonvulsant drug in the genetic model of seizure-prone DBA/2 mice. Our findings suggest that the anticonvulsant properties of felbamate depend upon its interaction with neurotransmission mediated by both the glycine/NMDA and the AMPA/kainate receptor complex.
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PMID:Excitatory amino acid neurotransmission through both NMDA and non-NMDA receptors is involved in the anticonvulsant activity of felbamate in DBA/2 mice. 752 82

The effect of midsagittal bisection of the brainstem (the midbrain to the pons) on amygdala (AM) kindling at the primary and the secondary sites was examined in rats. It was found that the kindling rate was not affected at either primary or secondary sites regardless of the extent of bisection. However, seizure progression beyond stage 4 bilateral clonus did not occur with extensive dorsal bisection. The findings suggest that the dorsal midline brainstem structure bisected in this study participates in the mechanism of stage 5 seizure but is not involved in the transhemispheric positive transfer mechanism in rodent AM kindling.
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PMID:Amygdala kindling in rats with brainstem bisection. 755 26

Metabotropic glutamate receptor (mGluR)-induced neuronal injury in the brain was further investigated in the rat. The highly selective mGluR agonist 1S,3R-1-aminocyclopentane-1, 3-dicarboxylic acid (1S,3R-ACPD) was infused stereotaxically into the left dorsal hippocampus of adult rats. Control (2 microliters saline injected) rats had minimal tissue injury that was confined to the area around the injection site. In contrast, a dose of 250 nmol/2 microliters 1S,3R-ACPD produced a moderate number of swollen and injured cells in polymorphic, pyramidal and molecular layers of the injected hippocampus which was observed at 4 and 8 h post-injection. However, at 24 h few injured or necrotic cells were found. A dose of 1000 nmol/2 microliters 1S,3R-ACPD produced severe cellular injury in polymorphic, pyramidal and molecular layers of the hippocampus at 4, 8, or 24 h. At 24 h after this higher dose of 1S,3R-ACPD, a number of necrotic cells (i.e. pyramidal neurons of area CA1) were found. Both doses of 1S,3R-ACPD produced seizures in animals that were characterized by multiple episodes of wet dog shakes, staring, immobility, facial automatisms, rearing, bilateral forelimb clonus, and loss of postural control. These data support a possible role for excessive mGluR activation in pathological states of convulsions and neurodegeneration.
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PMID:Reversible and irreversible neuronal injury induced by intrahippocampal infusion of the mGluR agonist 1S,3R-ACPD in the rat. 760 Jan 86

Mature DBA/2J (D2) and C57BL/6J (B6) mice aged 9-10 weeks were studied to determine susceptibility to behavioral seizures induced by kainic acid (KA) and the possible influence exerted by differences in metabolism and blood-brain barrier (BBB) transport. Mice were observed for 4 h after subcutaneous (s.c.) KA injection. Behavioral seizure parameters included latency to first seizure (clonus), latency to tonic/clonic seizure, and latency to status epilepticus (SE). At a KA dose of 25 mg/kg, 80% of D2 mice exhibited tonic/clonic seizures, whereas all B6 mice remained seizure-free. At 30 mg/kg, tonic/clonic seizures were observed in 100% of D2 mice and 25% of B6 mice. Of D2 mice exhibiting at least one clonic seizure in response to KA at a dose of 25 mg/kg, 50% entered SE and eventually died. Administration of [3H]KA (6.6 x 10(6) dpm) at doses of 25 mg/kg (convulsive) or 11.1 micrograms (nonconvulsive) to mice of both strains resulted in similar levels of radioactivity in cortex, hippocampus, and cerebellum 30 and 60 min after injection. Bioconversion of [3H]KA to a radiolabeled brain metabolite in vivo could not be documented in mice from either strain. Results confirm previously reported differences between D2 and B6 mice in their relative susceptibility to seizures induced by systemic KA administration and suggest that these differences are not related to strain-specific variation in metabolism or BBB transport of KA. Further studies of these two strains of mice may be useful for investigating genetic influences upon seizure susceptibility.
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PMID:Differential susceptibility to seizures induced by systemic kainic acid treatment in mature DBA/2J and C57BL/6J mice. 761 15


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