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

The anticonvulsant action of nitrous oxide and its time course were studied in rats. Bicuculline, a GABA-receptor antagonist, was administered intravenously at a rate of 0.2 mg.kg(-1).min(-1) during exposure to air (n = 60) or 75% nitrous oxide in oxygen (n = 80). The convulsant dose of bicuculline was determined. The rats were divided into subgroups according to the duration of exposure to air or nitrous oxide, from 0 to 120 min at 15 min intervals. Although the convulsant dose of bicuculline was consistent in the air group (1.03 +/- 0.06 mg.kg(-1), mean +/- SEM), it showed two peaks at 30- and 90 min exposures to nitrous oxide. The threshold dose in the nitrous oxide group was significantly higher than in the air group at only 15- and 30 min exposures (1.50 +/- 0.16, 2.15 +/- 0.25 mg.kg(-1), respectively, P < 0.05). We conclude that nitrous oxide has an anticonvulsant action against bicuculline-induced seizure, and that a cyclic nature exists in its action.
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PMID:Cyclic alteration in the anticonvulsant effect of nitrous oxide in rats. 1523 61

Although reduced calcium binding protein (CBP) immunoreactivities in the epileptic hippocampus have been well established, it has been controversial that these changes may directly indicate neuronal degeneration. In the present study, therefore, we investigated CBP expressions in the gerbil hippocampus following treatment with gamma-aminobutyric acid (GABA) receptor antagonists in order to assess whether altered CBP expressions are the result of either abnormal excitation or indicative of neuronal damage/degeneration. Seizure-sensitive (SS) gerbils showed a loss/decline of CBP immunoreactivities in some hippocampal neurons as compared with seizure-resistant (SR) gerbils. In muscimol (GABA(A) receptor agonist) treated SS gerbils, expression levels of CBP were enhanced as compared with saline-treated SS gerbils. Bicuculline (a GABA(A) receptor antagonist) treatment markedly reduced CBP immunoreactivities in hippocampal neurons of the SR gerbil. Baclofen (a GABA(B) receptor agonist) treatment increased CBP immunoreactivities in the hippocampus of SS gerbils, although its effect was lower than that of muscimol treatment. Moreover, phaclofen (GABA(B) receptor antagonist) treated SR gerbil showed reduction in calbindin D-28K immunoreactivity, not parvalbumin immunoreactivity, in the hippocampus. These findings therefore suggest that reduced CBP immunoreactivities may be the consequence of abnormal discharge caused by loss of GABAergic inhibition rather than an indication of the neuronal damage/degeneration.
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PMID:Effects of GABAergic transmissions on the immunoreactivities of calcium binding proteins in the gerbil hippocampus. 1577 49

Progestins can have antiseizure effects; however, the mechanisms and sites of action of these effects are not well-understood. Whether progesterone's actions at GABA(A) receptors in the hippocampus are important for its antiseizure effects was investigated. In Experiment 1, ovariectomized rats were administered sesame oil vehicle or a regimen of progesterone (500 microg sc, which produces physiological concentrations in plasma and the hippocampus), followed 2.5 hours later by administration of saline vehicle or a regimen of bicuculline (1 mg/kg, sc), a GABA(A) receptor antagonist, which does not produce any intrinsic effects on seizures. Progesterone, compared with vehicle, significantly increased the latency to, and decreased the number of, pentylenetetrazole-induced tonic seizures and increased GABA-stimulated chloride flux. Co-administration of bicuculline attenuated progesterone's antiseizure effects and decreased GABA-stimulated chloride flux in the hippocampus. Bicuculline did not alter ictal behavior compared with vehicle. In Experiment 2, ovariectomized rats were subcutaneously administered sesame oil or progesterone (500 microg), followed 2.5 hours later by bilateral infusions of bicuculline (100 ng) or vehicle (saline) into the hippocampus. Infusion of bicuculline into the hippocampus of progesterone-primed rats significantly increased ictal activity, compared with that induced by progesterone administration alone, but alone did not alter seizures compared with that produced by saline infusions into the hippocampus. These data suggest that actions of progesterone at GABA(A) receptors in the hippocampus are important for progesterone's antiseizure effects.
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PMID:Actions at GABA(A) receptors in the hippocampus may mediate some antiseizure effects of progestins. 1582 Mar 38

The role of GABAergic mechanism in the convulsant effect of mefloquine was investigated in mice. Mefloquine dose dependently induced tonic seizures in mice. Aminooxyacetic acid, diaminobutyric acid and muscimol significantly protected mice against mefloquine-induced seizures by significantly delaying the onset and decreasing the incidence of the seizures. Bicuculline and picrotoxin significantly enhanced the seizure producing effect of mefloquine and also significantly antagonised the protective effect of muscimol against the seizures. Phenobarbitone and diazepam effectively protected mice against mefloquine-induced seizures. Phenytoin did not alter mefloquine-induced seizures. These data indicate that GABA mechanisms might be involved in seizures produced by mefloquine in mice.
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PMID:Gamma-aminobutyric acid and mefloquine-induced seizures in mice. 1600 80

Overexcitation of neuronal networks in some forebrain structures and pathological synchronization of neuronal activity play crucial role in epileptic seizures. Seizure activity can be elicited experimentally by different convulsants. Because of various distribution of excitatory and inhibitory connections in the neocortex there might be laminar differences in seizure sensitivity. Current source density (CSD) analysis or immunocytochemical c-Fos localization offer suitable tools to localize increased activation of neurons during seizure. In the present experiments, interictal epileptiform activity elicited by 4-aminopiridine, bicuculline or Mg(2+)-free solution was recorded with a 16-channel multielectrode assembly in different layers of the somatosensory cortex, and CSDs were calculated. Parallel c-Fos immunocytochemistry was applied. Each convulsant elicited characteristic activation pattern. 4-aminopiridine induced relatively short discharges, which were associated with a huge sink in layer V, the sink and source pattern was relatively simple. Mg(2+)-free solution elicited the longest discharges, sinks appeared typically in the supragranular layers II and III than quickly distributed toward layers V and VI. Bicuculline induced rather similar seizure pattern as Mg(2+)-free solution, but the amplitudes of field potentials were larger, while the durations shorter. The peak of c-Fos activation, however, was not parallel with the largest electrical activation. Larger amount of stained cells appeared in layers II and III in 4-aminopiridine and bicuculline, respectively. In Mg(2+)-free solution the highest c-Fos activity was detected in upper layer VI. Long-lasting cellular effects do not always correspond to the largest electrical responses, which are primarily determined by the activation of asymmetrical pyramidal neurons. Interneurons, which possess more symmetric process arborisation, play less important role in the generation of field potentials, although they may be intensively activated during seizure.
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PMID:Laminar analysis of initiation and spread of epileptiform discharges in three in vitro models. 1653 65

Carbamazepine (CBZ) aggravates many generalized seizures types, particularly absence seizures, but the mechanisms underlying this are poorly understood. GABA signaling within the reticular nucleus (Rt) and the ventrobasal complex (VB) of the thalamus is critical to the neurophysiology of absence seizures. The hypothesis that CBZ aggravates absence seizures by acting at the VB thalamus via a GABA(A) receptor-mediated mechanism was investigated in a genetic rat model, generalized absence epilepsy rats from Strasbourg (GAERS). Seizure activity was quantified by a 90-min electroencephalogram recording postdrug injection. Intracerebroventricular injections of CBZ (15 microg in 4 microl) resulted in seizure aggravation versus vehicle treatment, with a mean increase in seizure time of 40%. This indicates that CBZ acts directly, rather than via a metabolite, on the brain to aggravate seizures. Seizure aggravation also occurred following bilateral microinjection of CBZ (0.75 microg in 0.2 microl) into the VB (53%) but not following injection into the Rt (-9%). However, seizure aggravation was blocked when the GABA(A) receptor antagonist, bicuculline (BIC, 0.04 microg in 0.2 microl), was coinjected with CBZ into the VB. Injection of BIC alone (versus vehicle) into the VB also blocked seizure aggravation following systemic administration of CBZ (15 mg/kg i.p.). In vitro studies in Xenopus oocytes expressing recombinant GABA(A) receptors demonstrated that CBZ produced a dose-dependent potentiation of the GABA current at a physiological relevant concentration range (1-100 microM). These data demonstrate that CBZ acts at the VB thalamus to aggravate absence seizures in GAERS and that activation of GABA(A) receptors is critical to this effect.
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PMID:The mechanism of carbamazepine aggravation of absence seizures. 1689 79

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time-course and dose-response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4-88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD(50) value was 135.6 (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.
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PMID:Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice. 1754 62

The posterior part of the hypothalamus plays a vital role in the homeostatic processes of the internal environment, including blood pressure and heart rate regulation, by means of gamma-aminobutyric acid (GABA)ergic and glutamatergic neurotransmission. In this study we measured the extracellular levels of GABA and L-glutamic acid in the dorsomedial hypothalamic nucleus (DMH) and posterior hypothalamus (PH), following intracerebroventricular (i.c.v.) administration of bicuculline, a GABA(A)-receptor antagonist, in genetic absence epileptic rats from Strasbourg (GAERS), where heart rate, blood pressure, and EEG recordings were also collected simultaneously. The i.c.v. injection of bicuculline (0.3 nmol) produced no response in non-epileptic Wistar rats but caused an increase in mean arterial pressure in GAERS (P<0.01). Microdialysis experiments showed that L-glutamic acid increased in the DMH in GAERS after bicuculline administration (P<0.01). Additionally, extracellular GABA concentration decreased in the PH (P<0.05). Bicuculline suppressed the spike-and-wave discharges, the characteristic sign of absence seizures. All these results suggest that the bicuculline-induced blood pressure response is accompanied by changes in L-glutamic acid levels in the DMH and GABA levels in the PH, indicating a bicuculline hypersensitivity in the DMH and PH of GAERS that may make the GAERS display an altered mode of central cardiovascular regulation. These results suggest that the circuits affected in GAERS are not only restricted to the regions responsible for seizure generation but also present in the hypothalamus.
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PMID:Extracellular hypothalamic gamma-aminobutyric acid (GABA) and L-glutamic acid concentrations in response to bicuculline in a genetic absence epilepsy rat model. 1827 Apr 69

This study investigates the temporal dynamics of ictal electrical activity induced by injection of the GABA(A) receptor antagonist bicuculline, and the glutamate agonist kainic acid, into the CA3 area of hippocampus. Experiments were conducted in freely moving adult Wistar rats implanted with microelectrodes in multiple brain areas. Wide-band electrical activity (0.1-3000 Hz) was recorded, and the latency of seizure onset as well as the pattern of electrical activity were investigated for each drug. The latencies between injection and the occurrence of first epileptiform events were 3.93 +/- 2.76 (+/-STD) min for bicuculline and 6.37 +/- 7.66 min for kainic acid, suggesting the existence of powerful seizure-suppressive mechanisms in the brain. Bicuculline evoked high-amplitude rhythmic epileptiform events at the site of injection which resembled interictal EEG spikes and rapidly propagated to adjacent and remote brain areas. Kainic acid evoked a completely different pattern with a gradual increase in the amplitude of 30-80 Hz activity. Whereas there was strong temporal correlation between EEG events at the site of bicuculline injection and discharges in distant areas, much less correlation was seen with kainic acid injection. Both patterns were followed by generalized ictal EEG discharges and behavioral seizures. Our results illustrate that the same area of the brain can trigger seizures with different electrographic patterns. The knowledge of the network mechanisms underlying these two distinct electrographic patterns might be helpful in designing differential strategies for preventing seizure occurrence.
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PMID:The cause of the imbalance in the neuronal network leading to seizure activity can be predicted by the electrographic pattern of the seizure onset. 1929 68

Generalized tonic-clonic seizures cause widespread physiological changes throughout the cerebral cortex and subcortical structures in the brain. Using combined blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) at 9.4 T and electroencephalography (EEG), these changes can be characterized with high spatiotemporal resolution. We studied BOLD changes in anesthetized Wistar rats during bicuculline-induced tonic-clonic seizures. Bicuculline, a GABA(A) receptor antagonist, was injected systemically and seizure activity was observed on EEG as high-amplitude, high-frequency polyspike discharges followed by clonic paroxysmal activity of lower frequency, with mean electrographic seizure duration of 349 s. Our aim was to characterize the spatial localization, direction, and timing of BOLD signal changes during the pre-ictal, ictal and post-ictal periods. Group analysis was performed across seizures using paired t-maps of BOLD signal superimposed on high-resolution anatomical images. Regional analysis was then performed using volumes of interest to quantify BOLD timecourses. In the pre-ictal period we found focal BOLD increases in specific areas of somatosensory cortex (S1, S2) and thalamus several seconds before seizure onset. During seizures we observed BOLD increases in cortex, brainstem and thalamus and BOLD decreases in the hippocampus. The largest ictal BOLD increases remained in the focal regions of somatosensory cortex showing pre-ictal increases. During the post-ictal period we observed widespread BOLD decreases. These findings support a model in which "generalized" tonic-clonic seizures begin with focal changes before electrographic seizure onset, which progress to non-uniform changes during seizures, possibly shedding light on the etiology and pathophysiology of similar seizures in humans.
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PMID:Focal BOLD fMRI changes in bicuculline-induced tonic-clonic seizures in the rat. 2007 42


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