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

Development of clonic-tonic flurothyl-induced seizures was examined in both normal and genetically epilepsy-prone rats (GEPRs). At each age, from 10 to 30 days, clonus occurred at significantly shorter latencies in GEPRs than in normal rats. The latency to onset of clonic seizures did not change with age, however, in either GEPRs or normal rats. A different pattern of response was observed in the progression to tonic seizures. As normal animals matured, the latency to tonic seizures became longer and, by day 30, the duration of flurothyl exposure necessary to induce tonus was almost 70% greater in normal rats than in the GEPRs. In contrast, in GEPRs, tonic extension occurred immediately following the onset of clonus throughout development. A subset of GEPRs failed to have audiogenic seizures in a 40-day posttest. These animals had a flurothyl response identical to their audiogenic-susceptible litter mates. These data suggest that (a) a protective mechanism which develops against tonic seizures in normal rats fails to mature in the GEPR, and (b) seizure inducing gene-linked neural abnormalities occur in the GEPR independent of pathologies underlying audiogenic seizures.
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PMID:Developing genetically epilepsy-prone rats have an abnormal seizure response to flurothyl. 291 11

Studies suggest that the 1,5-benzodiazepine clobazam possesses a favorable anticonvulsant profile due to its minimal neurotoxicity. The anticonvulsant and motor impairment effects of clobazam and 2 1,4-benzodiazepine, diazepam and clonazepam, were compared by dose-response analysis in amygdala-kindled rats and on 3 tests of motor function: gross motor impairment, a vertical screen test, and muscle tone. All drugs produced a significant, dose-dependent decrease in the duration of both behavioral and electrographic kindled seizure measures. Forelimb clonus suppression was the most sensitive measure of anticonvulsant drug effect. The order of potency for all effects was clonazepam greater than diazepam greater than clobazam. ED50s for the benzodiazepines' effects on motor impairment were compared to their ability to protect rats from forelimb clonus. Different spectrums of action for the various benzodiazepines were found depending on the comparison measure. Clonazepam had the most favorable ratio of potency for anticonvulsant vs. motor impairment activity when ataxia rating was the comparison measure. Diazepam had the most advantageous profile when the more sensitive screen test was used for comparison. Clobazam was not found to have a superior spectrum of action when compared across these measures. The results emphasize the importance of dose-response analyses and the consideration of behavioral measures used to assess beneficial and adverse effects of anticonvulsants.
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PMID:A comparison of the anticonvulsant effects of 1,4- and 1,5-benzodiazepines in the amygdala-kindled rat and their effects on motor function. 291 46

Unilateral intrastriatal injection of quinolinic acid (2,3 pyridine dicarboxylate; QUIN) in the rat produces episodic barrel rotations and tonic-clonic forepaw movements, lasting for several hours. We investigated whether intraperitoneal posttreatment with anticonvulsants could abolish this phenomenon when it is already fully developed, and whether their potency ratio was similar in models of epilepsy. All 8 tested antiepileptics, namely carbamazepine, clonazepam, diazepam, diphenylhydantoin, ethosuximide, flunarizine, phenobarbital and sodium valproate decreased this behaviour in a dose-dependent way. Six other drugs with anticonvulsant properties were also effective: DL-2-amino-7-phosphonoheptanoic acid, desipramine, etomidate, ketamine, meprobamate and sabeluzole. The ED50-values for halving the frequency of the episodes of barrel rotation correlated well with published ED50-values for inhibition of tonic hindpaw extension in the maximal metrazol seizure test (rs = .95, p less than 0.001) and with the ED50-values for halving the duration of the forepaw clonus in the rat-kindling model (rs = .93, p less than 0.001). This quinolinic acid test allows visualization of the onset of action of anticonvulsants, with each animal as its own control. In order to assess whether this test is also sensitive to drugs influencing the symptoms of Huntington's disease, the effect of the dopamine antagonists haloperidol and pimozide, the acetylcholinesterase inhibitor physostigmine and the anticholinergics atropine and dexetimide were investigated as well. The experiments suggested that the barrel rotations and clonic forepaw movements, only 3-6 hours after intrastriatal injection of QUIN respond to anticonvulsants, but are not specifically sensitive to drugs used in the symptomatic treatment of Huntington's disease.
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PMID:Episodic barrel rotations induced by intrastriatal injection of quinolinic acid in rats. Inhibition by anticonvulsants. 297 64

The purpose of the present investigation was to determine the possible role of GABAergic mechanism in the convulsant action of RO5-4864. Benzodiazepines (BZ) and other agents which facilitate central GABAergic transmission delayed the onset of facial and forelimb clonus, whereas tonic hind limb extension was blocked in a dose-dependent manner. RO5-4864-induced convulsions were blocked by diazepam, clonazepam, pentobarbital, ethanol and amino-oxyacetic acid (AOAA). RO5-4864-induced convulsions were not blocked by the BZ antagonist RO15-1788. Specifically, RO15-1788 caused a decrease in the onset of severity component of tonic seizures, which tended to become generalized and precipitated in a tonic extension of the hindlimbs. Further, subconvulsive doses of a direct GABA receptor antagonist, bicuculline, enhanced the proconvulsant action of RO5-4864, indicating thereby a potential antagonism of the central GABAergic transmission. These observations strongly suggest that RO5-4864 probably elicits convulsions by selective impairment of the GABAergic transmission.
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PMID:A possible role of a GABAergic mechanism in the convulsant action of RO5-4864. 299 8

The role of the inferior colliculus and GABAeric transmission within this structure in the development of susceptibility to sound-induced seizures in ethanol-dependent rats was examined. Ethanol-dependent rats with bilateral electrolytic lesions which destroyed approximately 50.0 +/- 6.4% of the inferior colliculus failed to exhibit susceptibility to sound-induced seizures. However, comparable medial geniculate body lesions (82.7 +/- 2.7% complete) did not alter wild running, slightly reduced tonus and actually increased clonus susceptibility in rats treated similarly with ethanol. As reported previously, bilateral injection of either muscimol (43-263 pmol/site) or racemic baclofen (520-1580 pmol/site) into the inferior colliculus also suppressed seizure susceptibility. Other studies in ethanol-naive animals found that bilateral microinfusion of (+)-bicuculline methiodide (2 or 20 pmol/min for up to 5 min) into the inferior colliculus induced wild running and clonus closely resembling sound-induced seizure responses in ethanol-dependent rats. Although similar microinjections of (+)-bicuculline methiodide (0.4 pmol/min for 5 min) into the inferior colliculus did not induce seizure activity directly, an increased susceptibility to sound-induced seizures was observed. Electrolytic lesions of the medial geniculate body did not block wild running responses induced by (+)-bicuculline methiodide, but slightly reduced clonus. Five-minute infusions of picrotoxin (200 pmol/min), Ro5-3663 (2000 pmol/min), kainic acid (20 or 200 pmol/min), strychnine (2000 pmol/min) or carbachol 2000 pmol/min) into the inferior colliculus of ethanol-naive rats all induced bicuculline-like seizures. Seizures induced by bicuculline methiodide, picrotoxin or Ro5-3663 occurred within 5 min after the start of infusions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:GABAergic modulation of inferior colliculus excitability: role in the ethanol withdrawal audiogenic seizures. 300 88

High amplitude spiking representative of seizures, accompanied by an unusual motor behavior pattern of rearing and forelimbic clonus resembling "boxing," was elicited by microinjection of the cholinergic agonist, carbachol, 4 micrograms, into the medial prefrontal cortex of the rat. A rating scale devised to score the behavior revealed a motor pattern elicited by carbachol from the medial anterior cortex which was similar to that described by Racine for electrical stimulation of the amygdala. Topographical analysis of the areas surrounding the medial anterior cortex region revealed that the motor manifestations of seizures were elicited over a wide region of the anterior cortex, with scores significantly lower at carbachol microinjection sites greater than 1 mm rostral, 2 and 3 mm caudal, and 2 mm lateral to the standard medial prefrontal cortex site. Unilateral microinjection of carbachol yielded motor seizures primarily from the contralateral forepaw, suggesting involvement of a crossed pathway. Retrograde tracing with fast blue dye, combined with immunostaining for choline acetyltransferase and NADPH-diaphorase, found that the cholinergic neurons innervating the standard microinjection site were the dorsolateral tegmental cells, as previously reported, which have been shown to also contain substance P and corticotropin releasing factor. In addition, cholinergic neurons of the nucleus basalis of Meynert region were found to innervate the standard microinjection site. These findings implicate cholinergic innervation of the rostral cortex in classical limbic seizures.
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PMID:Anatomical analysis of frontal cortex sites at which carbachol induces motor seizures in the rat. 317 34

Electrical stimulation of rat amygdala induced self-sustained steady-state seizures (status epilepticus (SE] within 60 min. These SE states varied in behavioral severity from mere alteration of motility to frank clonic convulsions. Four distinct behavioral states were observed: immobility, exploration, mastication and clonus. These SE states were associated with [14C]2-deoxyglucose (2-DG) autoradiography anatomic patterns that were correspondingly more extensive and complex. Four distinct 2-DG activation patterns were observed: a restricted pattern involving several discrete limbic nuclei, including amygdala; more extensive patterns involving numerous limbic areas, first unilaterally, then bilaterally; finally the most extensive pattern involving widespread areas of forebrain. These data imply a systematic progression of seizure activity: originating in the amygdala, then spreading to some direct amygdala projection areas, and from there to a restricted network of interconnected ipsilateral limbic nuclei. This restricted network then recruits most of the remaining limbic structures, first ipsilaterally, then contralaterally. Finally, most of the basal ganglia, thalamus and neocortex are recruited.
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PMID:Functional [14C]2-deoxyglucose mapping of progressive states of status epilepticus induced by amygdala stimulation in rat. 321 74

The sensitivity to intracerebroventricular morphine-induced convulsions was determined in members of the severe seizure (GEPR-9) and moderate seizure (GEPR-3) colonies of genetically epilepsy-prone rats as well as in non-epileptic control rats. GEPR-9s were more sensitive to morphine-induced wet-dog shakes, rearing with bilateral forelimb clonus and generalized clonus than controls of GEPR-3s. GEPR-3s were less sensitive to morphine-induced wet-dog shakes and rearing with bilateral forelimb clonus than controls. Both high and extremely low doses of morphine in GEPR-9s elicited tonic extensor convulsions resembling the characteristic sound-induced convulsion of GEPR-9s. The results suggest that opiotergic systems may contribute to the pathophysiology of the seizure-prone condition in GEPR-9s. Further, differences in responsiveness of opiotergic systems in GEPR-3s and GEPR-9s may partially account for differences in seizure severity in the characteristic sound-induced seizures of these two types of GEPRs.
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PMID:Responsiveness of genetically epilepsy-prone rats to intracerebroventricular morphine-induced convulsions. 336 37

A strain of Wistar rats was inbred for susceptibility to audiogenic seizures characterized by one or two wild running fits followed by tonic dorsiflexion with open mouth and then a catatonic state. During the tonic phase, the cortical EEG was flat for 1 to 2 sec, then changed to a slow, regular low-amplitude discharge, 9 to 12 c/s, for 25 to 60 sec. In these rats exposed to 40 daily 90-sec auditory stimuli, behavior and EEG changed. The wild running became disorganized by myoclonic jerks of the limbs and body. In some animals, the tonic extension disappeared and a myoclonic seizure developed progressively, with facial and forelimb clonus, and rearing and falling. In others, the tonic phase was followed by a generalized clonic phase. The EEG during the myoclonic and tonic-clonic seizures showed high-amplitude rhythmic spikes, polyspikes and spike-waves, 1 to 10 c/s, for 40 to 120 sec, often outlasting the sound stimulus. The effects of ethosuximide, carbamazepine and phenytoin were the same on primary and modified audiogenic seizures. The progressive behavioral and EEG modifications of audiogenic seizures following repeated auditory stimuli suggest that kindling had developed, the seizures being propagated from the brain stem to forebrain structures.
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PMID:Audiogenic seizures in Wistar rats before and after repeated auditory stimuli: clinical, pharmacological, and electroencephalographic studies. 341 35

Subcutaneous treatment of rats with low doses of lithium and pilocarpine or a high dose of pilocarpine results in a severe seizure--brain damage syndrome. Rats thus treated were studied with multiple-depth electrodes, quantitative [14C]2-deoxyglucose autoradiography, and light and electron microscopy. Rats receiving lithium-pilocarpine did not differ from high-dose pilocarpine rats in behavioral, electrographic, metabolic or histopathological findings, but lithium-pilocarpine reproduced the syndrome more reliably and with a lower acute mortality rate. Organized electrographic seizure activity developed just prior to the onset of behavioral forelimb clonus and appeared to originate from ventral forebrain in the vicinity of the ventral pallidum and/or nucleus accumbens. From these sites activity spread rapidly to involve other regions. Once initiated, electrographic seizures persisted for hours. Increased glucose utilization was found in most brain regions during the period of continuous seizure activity. The greatest increases were found in the ventral pallidum, globus pallidus, hippocampus, entorhinal cortex, amygdala, lateral septum, substantia nigra, ventrobasal and mediodorsal thalamus and frontal motor cortex. Animals sustaining seizures displayed a disseminated pattern of neural degeneration not involving globus pallidus or ventral pallidum but otherwise coinciding with the above pattern of enhanced glucose utilization. No consistent correlation was observed between the pattern of brain damage and known regions of high muscarinic cholinergic receptor density. Ultrastructurally, the cytopathological changes, like those associated with various other sustained seizure syndromes, resemble the excitotoxic type of damage glutamate is known to cause. This seizure-brain damage syndrome and that induced by systemic kainic acid appear to be similar in behavioral but not in electrophysiological or metabolic manifestations. During kainic acid seizures, electrographic changes are first recorded in the hippocampus while they are first detected in the ventral forebrain region in pilocarpine seizures. Pilocarpine also induced metabolic activation of ventral forebrain sites not activated by kainic acid. The cytopathology associated with the two syndromes is identical in type but not in pattern, the cholinergic model being characterized by much greater neocortical and slightly less hippocampal damage. Further study of these cholinergic models may provide new insights into the roles of the major excitatory neurotransmitter systems (cholinergic and glutamergic) in limbic epilepsy.
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PMID:The functional anatomy and pathology of lithium-pilocarpine and high-dose pilocarpine seizures. 343 96


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