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

The acute anticonvulsant efficacy of diazepam (1.5 mg/kg, i.p.) was evaluated by repeated test injection in kindled rats subcutaneously implanted with diazepam-filled or empty silastic tubes for 3 weeks. Tolerance developed to acute test injections in both diazepam- and sham-implanted rats. Tolerance developed to a lesser extent in another group of diazepam-implanted rats which did not receive acute intermittent anticonvulsant tests. The hypothesis that contingent tolerance had developed to the anticonvulsant actions of benzodiazepines (diazepam, 1.5 mg/kg, i.p. and clobazam, 10 mg/kg, i.p.) in kindled rats given acute intermittent injections was investigated using a 'before-after' design. Significant contingent tolerance developed in rats which received intermittent benzodiazepine treatment before, but not after, amygdala stimulation. Tolerance developed to different extents depending on the seizure measure evaluated (forelimb clonus duration, amygdala afterdischarge duration, motor seizure latency and duration, and seizure stage). Contingent tolerance to both benzodiazepines developed at a similar rate. The findings suggest that contingent tolerance may contribute a sizeable component to the overall functional benzodiazepine tolerance measured in long-term anticonvulsant drug studies in kindled rats. Several questions regarding contingent tolerance phenomena are posed and the implications of these findings for studies using repeated anticonvulsant testing are discussed.
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PMID:Repeated anticonvulsant testing: contingent tolerance to diazepam and clobazam in kindled rats. 161 82

Experiments examining seizure sensitivity were conducted on adult male offspring exposed to diazepam at 1.0 or 2.5 mg/kg per day in utero over gestational days 14-20. Threshold dosages to facial clonus, myoclonic jerk, clonic seizure, and extensor tonus were determined via i.v. infusion of bicuculline, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), picrotoxin, pentylenetetrazol, caffeine and strychnine. Relative to uninjected and vehicle-exposed adult male offspring, prenatal diazepam administration reduced the threshold for bicuculline- and DMCM-induced facial clonus and myoclonic jerk by 40-50%. The threshold dosages to facial clonus, myoclonic jerk and clonic seizure from picrotoxin infusion were similarly reduced in animals exposed to diazepam in utero. In contrast, seizure thresholds to pentylenetetrazol, caffeine and strychnine were not affected by early developmental exposure to diazepam. In parallel biochemical studies, an increased sensitivity to the antagonistic effects of bicuculline methiodide on gamma-aminobutyrate (GABA)-stimulated chloride influx was observed in cortical synaptoneurosomes from adult male progeny of diazepam-treated dams. The results are interpreted to reflect a long-lasting alteration in the function of the GABA/benzodiazepine receptor complex by prenatal diazepam exposure that is manifest at the behavioral and neurochemical level in a pharmacologic specific manner.
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PMID:Gestational exposure to diazepam increases sensitivity to convulsants that act at the GABA/benzodiazepine receptor complex. 165 53

The tetanus toxin model of epilepsy, involving direct microinjection of toxin into the mammalian brain, has a number of advantages relative to other chronic models. However, chronic seizure foci have been confined primarily to the hippocampus. In the present study, 5 cats received total doses of 7.5-22.5 ng of tetanus toxin applied to the left primary motor cortex through an epidural cannula. After 2-18 days, all 5 cats exhibited similar persistent epileptiform syndromes. Three distinct types of spontaneous seizures were noted: focal motor seizures of variable complexity, focal motor seizures with secondary generalization, and epilepsia partialis continua. All cats required anticonvulsant therapy. Simple focal motor seizures, which predominated, were electrographically characterized by 3-5 Hz spike-sharp wave activity, originating in the left motor cortex, associated with contralateral shoulder and forepaw clonus and jacksonian spread. Electrographic activity quickly spread to ipsilateral neocortical structures, and in longer episodes to the cingulate gyri. Seizure foci were still active as long as 37 days after toxin injection. Light microscopic damage attributable to the toxin was absent. These experiments further generalized the tetanus toxin model and confirmed its advantages.
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PMID:Chronic focal epilepsy induced by microinjection of tetanus toxin into the cat motor cortex. 169 99

Ictal, postictal and interictal electrical activities were recorded in the posterior cingulate cortex and hippocampus in the rat following kindling stimulations in the cingulate cortex. The afterdischarges (ADs) consisted of fast spikes and slow spike-and-wave of 2-5 Hz. Initial motor signs typically consisted of extension of the forelimbs and head, followed by clonic fore- and/or hind limb movements; there was no consistent laterality in any of the motor signs. Electrodes at or near the cingulum or corpus callosum ('white matter' group) gave kindling rates faster than other sites in the 'grey matter' of cingulate cortex (area 29); 2 of 7 animals had first-trial generalized motor seizures. The 'white matter' group averaged 4.6 ADs to reach the first 'bilateral forelimb clonus,' as compared to 17.8 ADs for the 'grey matter' group. The frequency and morphology of sharp EEG spikes in the cingulate cortex remained largely unchanged during the course of kindling. Cingulate interictal spikes were infrequent. The intimate connections of the cingulate cortex to motor and limbic structures rather than its intrinsic circuitry may be important for its fast kindling rates.
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PMID:Kindling in the posterior cingulate cortex: electrographic and behavioral characteristics. 169 45

A 23-year-old woman who had an uneventful prenatal course and normal delivery developed severe, generalized headache and blurred vision on postpartum day four. The patient was noted to have generalized hyperreflexia and sustained ankle clonus. The blood pressure was 170/100 mm Hg, there was no edema, and the urine showed trace proteinuria. The visual disturbance rapidly progressed to complete blindness with preserved pupillary reactions. The patient then had a generalized tonic-clonic seizure lasting about one minute. Treatment was initiated with intravenous diazepam and phenytoin, and there was no recurrence of seizure activity. Vision returned to normal and the patient made a complete recovery. This case is presented to demonstrate progressive postpartum pre-eclampsia and the importance of early recognition and treatment. Pathophysiologic mechanisms and treatment options are discussed.
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PMID:Cortical blindness in postpartum preeclampsia progressing to eclampsia: case report. 173 43

The rate at which SJL/J mice recover susceptibility following an initial sound-induced seizure was examined. Fewer than 15% of the subjects seized when retested after a 2-min delay, and only 50% reseized after a 10-min delay. The likelihood of a second seizure was enhanced if the initial seizure exhibited a rapid progression to clonus. During the retest, seizures progressed more slowly than during the initial test, which indicates that recovery was not complete even if a second seizure was induced. Finally, recovery of seizure susceptibility was prevented as long as the subject continued to be exposed to intense auditory stimulation following the initial convulsion, an effect previously noted by Alexander and Kopeloff (1980). The findings are discussed in terms of a recently proposed central inhibitory model of the recovery of audiogenic seizure susceptibility.
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PMID:Recovery of susceptibility following audiogenic seizure in mice. 175 83

Acute and chronic lithium treatment reduces levels of brain myo-inositol in rats. Several biological effects of lithium can be reversed in vitro by addition of myo-inositol. The ability of myo-inositol to reverse behavioral effects of lithium was tested using chronic inositol administration or acute intracerebroventricular (i.c.v.) injections. Chronic myoinositol elevated activity during the first 10 min in an open field, but did not reverse lithium-induced hypokinesia. Myo-inositol (i.c.v.) reversed the suppression of rearing behavior 24 hrs after an acute dose of lithium (5 mEq/kg) but did not attenuate hypokinesia 24 hrs after a high dose of lithium (10 mEq/kg). Myo-inositol, but not the inactive isomer chiro-inositol (i.c.v.), also significantly prolonged the latency to clonus in the lithium pilocarpine seizure model. These studies suggest that reduction of brain myo-inositol may be a critical mechanism for the behavioral effects of lithium.
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PMID:Myo-inositol attenuates two specific behavioral effects of acute lithium in rats. 177 87

The beta-carbolines, methyl-beta-carboline-3-carboxylate (beta-CCM) and 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) are known to have pharmacological properties opposite to those of agonistic benzodiazepines. Convulsions induced by these drugs lead to differential patterns, such as clonus, myoclonic or tonic seizures. In 10 different inbred strains of mice we investigated whether the responsiveness to the two drugs was the same, irrespective of the pattern of convulsions. We found the same ranking in the responsiveness of the strains to both drugs in the case of myoclonic seizures. No such correlation could be found for clonus or tonic seizures. Our conclusion is that the same genetic factors determine myoclonic seizures, whereas a plurality of mechanisms underly the other patterns. Thus, myoclonic seizures seem to be the most appropriate index for evaluating the convulsant action of beta-carbolines in genetic experiments.
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PMID:Comparisons between patterns of convulsions induced by two beta-carbolines in 10 inbred strains of mice. 179

The anticonvulsant profiles of two potent and orally active gamma-aminobutyric acid (GABA) uptake inhibitors, 1-(4,4-diphenyl-3-butenyl)-3-piperidine-carboxylic acid hydrochloride (SK&F 89976-A) and 1-(4,4-diphenyl-3-butenyl)-1,2,5,6-tetrahydro-3-pyridine-carboxylic acid hydrochloride (SK&F 100330-A), were determined with a battery of well-standardized tests in mice and rats and compared with the profiles of phenytoin (PHT), carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) when subjected to the same tests. ED50 values were calculated and compared with TD50 values for minimal motor impairment to provide protective indexes (PI = TD50/ED50). The anticonvulsant profiles of SK&F 89976-A and SK&F 100330-A were similar and suggest that these compounds raise the threshold for seizure initiation rather than inhibit seizure spread. Like intraperitoneal (i.p.) PHT, CBZ, VPA, and CZP, SK&F 89976-A and SK&F 100330-A inhibited seizures in corneally kindled rats. The profiles of SK&F 89976-A and SK&F 100330-A were most similar to that of CZP and virtually opposite to that of PHT. Intraperitoneal SK&F 100330-A provided complete protection against pentylenetetrazol-induced seizures [subcutaneous (s.c.) PTZ] in mice but was ineffective against seizures induced by maximal electroshock (MES) at doses slightly greater than its TD50. SK&F 100330-A provided complete protection against picrotoxin-induced seizures (s.c. Pic) and against both clonus and forelimb tonic extension induced by NMDA N-methyl-D-aspartate [intracerebral ventricular (i.c.v.)-NMDA] in mice; however, SK&F 100330-A was ineffective against seizures induced by bicuculline (s.c. Bic) and strychnine (s.c. Strych) at doses slightly greater than its TD50. SK&F 89976-A was similar but provided partial protection against NMDA-induced clonus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Anticonvulsant profiles of the potent and orally active GABA uptake inhibitors SK&F 89976-A and SK&F 100330-A and four prototype antiepileptic drugs in mice and rats. 183 Nov 22

The effect of lamotrigine, a novel potential antiepileptic drug, upon the development of kindled cortical seizures was investigated in rats. Although lamotrigine, at all doses tested, failed to block or reduce the rate of development of kindling, it did have a profound effect upon the production of both non-kindled and kindled responses. All doses (3, 6, 12 and 18 mg/kg) produced a significant increase in the number of nil responses (where stimulation failed to evoke a behavioural clonus or afterdischarge) and a decrease in non-kindled responses. Doses of 12 and 18 mg/kg also significantly reduced the number of kindled responses and the duration of the kindled seizure. It is suggested that these effects of lamotrigine result from its ability to inhibit the release of glutamate, an excitatory amino acid which has been implicated in the production of kindled seizures. In contrast to previous studies on the development of kindling, it was found that in the groups which received either 12 or 18 mg/kg lamotrigine, it was possible to produce kindling without evoking any nonkindled afterdischarge. This finding is discussed in the light of the current theories surrounding the kindling process. This study suggests that lamotrigine, as well as possibly being of value in the treatment of complex partial and generalised (tonic-clonic) seizures, may also be of value in the treatment of elementary (simple) partial seizures.
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PMID:The effect of lamotrigine upon development of cortical kindled seizures in the rat. 185 61


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