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

Changes in cardiodynamics and regional blood flow were examined in chronically prepared paralyzed cats during seizures induced electrically by transcerebral or direct cortical stimulation or by administration of flurothyl ether (Indoklon) or pentylenetetrazol (Metrazol). Transcerebral and chemical stimuli produced the greatest vascular responses. During seizures there was an abrupt elevation of arterial pressure unassociated with consistent changes in heart rate. Vascular resistance was increased in femoral, renal and mesenteric arteries with variable reductions in blood flow. Resistance was decreased and flow passively increased in the common carotid artery reflecting the loss of cerebral autoregulation. Cardiac output was unchanged. With seizures associated with large elevations of arterial pressure, the central venous and left ventricular end-diastolic pressures were markedly increased indicating incipient congestive failure. The pressor response was blocked by alpha-adrenergic blockade with phentolamine. Increased regional vascular resistance was abolished by regional sympathectomy. While either adrenalectomy or treatment with 6-hydroxydopamine alone failed to abolish the pressor response, combined, they did. Such treatment unmasked an atropine-sensitive bradycardia. The pressor response with seizures is a consequence of increased vascular resistance in viscera and muscles due to widespread activation of sympathetic neurons and release of adrenomedullary catecholamines. Co-activation of cardiovagal and cardiosympathetic neurons may underlie some associated arrhythmias. Cardiovascular events may severe, by redistribution of the cardiac output, to assure increased availability of oxygen and nutrients to brain to meet the metabolic demands of convulsions.
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PMID:Changes in regional blood flow and cardiodynamics associated with electrically and chemically induced epilepsy in cat. 113 82

25 Wistar rats were subjected twice daily to epileptic seizures induced by the convulsant gaz Flurothyl. Compared with littermates of the same sex and birth weight, the brain of seizure-treated rats showed a reduction of 6% (5.2 million cells) after 5 days and 17.6% (33.4 million cells) after 10 days of treatment.
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PMID:Developmental brain damage after chemically induced epileptic seizures. 119 96

The substantia nigra GABAergic system is considered important for the modification of seizures. Our previous studies have shown that, in rat pups, nigral infusions of baclofen suppressed flurothyl-induced seizures. In the present study, we determined, in rat pups, the effect of nigral infusions of gamma-vinyl-GABA (GVG) on clonic-tonic seizures induced by flurothyl, generated a dose-response curve of the GVG effect and investigated the possible role of the nigral GABAA receptor in mediating the GVG effect. Bilateral nigral infusions of GVG profoundly suppressed flurothyl-induced tonic seizures in a dose-dependent fashion. Flurothyl-induced clonic seizures were not modified. The lowest effective dose of nigral GVG administration was 5 micrograms/0.25 microliter per site. Nigral infusions of GVG at doses greater than 10 micrograms/0.25 microliter induced sedation as well. Infusions of GVG, 2 mm dorsal to the substantia nigra, did not alter seizure latencies. Bilateral nigral infusions of bicuculline, a specific GABAA receptor antagonist, reduced the protective potency of GVG against flurothyl-induced seizures. Nigrally administered muscimol, a GABAA receptor agonist, also attenuated the anticonvulsant effect of GVG. These findings suggest that the optimal dose of nigrally infused GVG against flurothyl-induced seizures is in the range of 5-10 micrograms/0.25 microliter and that GVG may be more efficient as an anticonvulsant for the treatment of tonic seizures in developing animals. The anticonvulsant effect of GVG may, in part, involve the nigral GABAA receptor. The data, together with the previous experiments, indicate that both nigral GABAA and GABAB receptors may play a role in the regulation of seizures in rat pups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Is the anticonvulsant effect of substantia nigra infusion of gamma-vinyl-GABA (GVG) mediated by the GABAA receptor in rat pups? 164 27

Perioperative seizures have numerous potential etiologies. In general, when seizures occur during surgery, their onset often coincides with the introduction of a specific anesthetic or analgesic drug. Conversely, postoperative seizures are more commonly due to nonanesthetic causes. However, there have been reports of postoperative convulsions that appeared to be caused by anesthetic or analgesic drugs administered intraoperatively via inhalation or injection (e.g., intravenous, epidural, or peripheral nerve block). Some anesthetics appear to possess both proconvulsant and anticonvulsant properties. One possible factor is an inherent pharmacodynamic variability in the responsiveness of inhibitory and excitatory target tissues in the CNS. This is well illustrated by the anticonvulsant and proconvulsant effects of progressively higher doses of local anesthetic drugs. This variability in neuronal responsiveness could also explain the conflicting findings for low versus high doses of fentanyl and etomidate. Furthermore, biological variation in the individual patient's responsiveness to certain anesthetic drugs could be an additional contributory factor. Differing structure-activity relationships might also explain why some anesthetic agents possess both proconvulsant and anticonvulsant properties. Relatively minor modifications in a drug's structure can influence its affinity for a specific receptor site and its intrinsic pharmacologic activity. For example, when methohexital was first introduced, convulsions were commonly encountered in patients with and without a history of epilepsy. Subsequent fractionation of the original compound into its two isomeric forms resulted in the identification of the isomer primarily responsible for this convulsive activity. In its present formulation (Brevital; Eli Lilly, Indianapolis, Ind.), the epileptogenic properties of methohexital are limited to patients with psychomotor epilepsy. However, compared with thiopental, excitatory effects are still more common with methohexital. The excitatory effects of methohexital are presumably due to its methylated structure. The inhaled anesthetic flurothyl (hexaflurodiethyl) ether and the intravenous anesthetic ketamine also illustrate how subtle changes in stereoisomerism can result in significant changes in structure-activity relationships. Flurothyl, a fluorinated ether analogue, reliably produces convulsions in nonepileptic patients, whereas its structural isomer isoindoklon has not been associated with seizure activity. Other examples of isomer or structural analogue relationships that produce differential effects on neuronal hyperexcitability include enflurane-isoflurane and meperidine-normeperidine. In conclusion, the patient population (epileptic or nonepileptic), the method of documentation (EEG study or clinical observation), and the method of EEG analysis (cortical or depth electrodes) must be considered to properly analyze the proconvulsant and/or anticonvulsant properties of an anesthetic or analgesic drug.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pro- and anticonvulsant effects of anesthetics (Part II) 240 Jan 25

Flurothyl-induced status epilepticus in the rat causes a hypermetabolic necrosis in the substantia nigra pars reticulata (SNPR). We studied if cortically generated excitatory input into the SNPR was causative of the structural damage. Rats were subjected to a unilateral frontal cortex lesion prior to induction of 40 min status epilepticus. A distinct mitigation in the size of the necrotic region in the ipsilateral SMPR was noted when compared to the contralateral side of the same animals (N = 10). No side difference was noted in animals where a lesion of similar size was placed in the parietal cortex region (N = 2) or in unlesioned animals subjected to seizures (N = 4). Neither analyses of energy metabolites in the cerebral cortex nor EEG revealed any side differences during seizures in the animals with lesions in the frontal cortex. This suggests that difference in seizure intensity was not the explanation for the mitigation of SNPR damage. It is suggested that the excitatory input from the frontal cortex was necessary for development of neuronal necrosis in the SNPR due to seizures.
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PMID:Seizure-induced damage in the substantia nigra pars reticulata: lesions in the frontal cortex prior to the seizure period mitigate the damage. 272 14

Monosodium glutamate (MSG) administration to neonatal rodents produces convulsions and results in numerous biochemical and behavioral deficits. These studies were undertaken to determine if neonatal administration of MSG produced permanent alterations in seizure susceptibility, since previous investigations were inconclusive. A flurothyl ether seizure screening technique was used to evaluate seizure susceptibility in adult mice that received neonatal injections of MSG (4 mg/g and 1 mg/g). MSG treatment resulted in significant reductions in whole brain weight but did not alter seizure threshold. A naloxone (5 mg/kg) challenge was also ineffective in altering the seizure thresholds of either control of MSG-treated mice. Flurothyl ether produced hypothermia which was correlated with the duration of flurothyl exposure; however, the relationship of hypothermia to seizure induction was unclear. Flurothyl seizure testing proved to be a rapid and reliable technique with which to evaluate seizure susceptibility.
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PMID:Flurothyl seizure thresholds in mice treated neonatally with a single injection of monosodium glutamate (MSG): evaluation of experimental parameters in flurothyl seizure testing. 368 52

delta-Aminolevulinic acid, an intermediate in heme formation, is elevated in certain human disorders including acute intermittent porphyria, tyrosinemia, and lead poisoning. It has been implicated in the central nervous system manifestations of these disorders via interactions with the GABAergic system. This potential interaction was examined by testing whether or not delta-aminolevulinic acid could alter the latency to seizure in mice. Seizures were induced in a variety of inbred strains of mice including C57BL, C3H, DBA mice and in a heterogeneous stock of mice. Flurothyl and 3-mercaptopropionic acid were used to induce seizures in the presence and absence of delta-aminolevulinic acid administered either i.p. (0.5 and 1.5 mmol/kg), or i.c.v. (4.5 and 450 nmol). delta-Aminolevulinic acid increased the latency to myoclonic and clonic seizures induced by flurothyl when administered i.p.; i.c.v. injections also delayed clonic seizures induced by flurothyl, and increased the latency to tonic seizures induced by 3-mercaptopropionic acid. The degree to which delta-aminolevulinic acid altered seizure latency in all tests was dependent on strain of mouse tested. These data support the conclusion that delta-aminolevulinic acid can act as an anticonvulsant agent, and mimic the effects of GABA. Moreover, there is genetic variation in the sensitivity of the various strains of mice to delta-aminolevulinic acid.
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PMID:Genetic differences in the effects of delta-aminolevulinic acid on seizure latency in mice. 377 Jan 19

Because of the critical role of excitatory amino acids (EAAs) in epileptogenesis and seizure-induced brain damage, EAA antagonists are now being considered as a possible therapy for seizures. However, during development EAAs play a pivotal role in learning, memory, and brain plasticity. To evaluate the long-term effects of a short course of EAA antagonists on the developing brain, a non-NMDA antagonist, NBQX, or a NMDA antagonist, MK-801, were administered over 7 days by osmotic pumps stereotaxically implanted into the lateral ventricles of normal 10 day old rats. Alternatively, 10 and 20 day old rats received a 7 day course of intraperitoneal (i.p.) NBQX. One month later, the NBQX-, MK-801-treated rats, and controls underwent a series of behavioral studies: handling test, open field, and Morris water maze. Flurothyl inhalation was used to test seizure susceptibility in all groups. Although all of the rats treated with NBQX via osmotic pumps has spontaneous seizure, rats surviving infusion of EAAs had no deficits in learning, memory, or behavior and did not differ from controls in seizure susceptibility with flurothyl. In the developing animal, a short-term course of EAA antagonists leads to no long-term adverse effects on behavior or seizure susceptibility.
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PMID:Long-term effects of excitatory amino acid antagonists NBQX and MK-801 on the developing brain. 887 1

Flurothyl kindling initiates a time-dependent process that results in a facilitated propagation from the forebrain to the brainstem seizure system and in an increase in the complexity of behavioral seizure expression. We investigated the involvement of the ventromedial nucleus of the hypothalamus (VMH) in mediating this facilitated propagation between these seizure systems. Bilateral ibotenic acid lesions of the VMH, but not the dorsomedial nucleus of the hypothalamus (DMH), resulted in a disruption in the propagation of seizure activity from the forebrain to the brainstem. Moreover, VMH lesioned mice were able to express brainstem seizures following minimal corneal electroconvulsive shock (mECS). Together, our results indicate that the VMH is a critical substrate involved in propagating seizure activity between the forebrain and brainstem, but is not involved in the expression systems necessary for forebrain or brainstem seizure manifestations.
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PMID:The role of the ventromedial nucleus of the hypothalamus in epileptogenesis. 985 70

We investigated the characteristics of the flurothyl-induced seizures and the effects of antiepileptic drugs on the flurothyl-induced seizure model in a previously untested Mongolian gerbil species. Mongolian gerbils demonstrated tonic extension immediately after or within 1 min after the appearance of clonic convulsion. Very high amplitude spike waves appeared in these regions concurrent with the appearance of clonic convulsion. When the tonic extension appeared immediately after the clonic convulsion, the high amplitude spike waves continued during tonic convulsion. When the tonic extension occurred, high amplitude spike waves appeared in these three regions within a very short time, and afterward Mongolian gerbils died. Administration of valproic acid-Na (200 mg/kg), ethosuximide (100 and 200 mg/kg), clonazepam (2 mg/kg) and diazepam (0.5, 1 and 2 mg/kg) significantly prolonged the latency of clonic convulsion. Zonisamide-Na, phenytoin and carbamazepine, however, had no such effect. In Mongolian gerbils, tonic extension was demonstrated immediately after the appearance of clonic convulsion, yet, this effect was inhibited by all these drugs in a dose-dependent manner. Diazepam completely blocked the appearance of any behavioral changes in animals. These findings suggest that diazepam has a significant effect on flurothyl-induced seizures. Flurothyl-induced convulsions are associated with GABA receptors; hence, benzodiazepine (BDP) suppression may result from the strong relation between BDP and GABAnergic neurons.
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PMID:Characteristics of flurothyl-induced seizures and the effect of antiepileptic drugs on flurothyl-induced seizures in Mongolian gerbils. 1237 61


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