Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pretreatment of adult male Sprague-Dawley rats with a single dose of gamma-vinyl GABA (GVG) (1200 mg/kg, IP) or gamma-acetylenic GABA (GAG) (100 mg/kg, IP) did not affect the threshold of metrazol-activated generalized seizures, but increased their duration to the point of status epilepticus. In rats with epilepsy kindled by amygdaloid stimulation, a single dose of GVG (800 mg/kg, IP) and five subsequent daily administrations of GAG (80 mg/kg, IP) tended to reduce the motor manifestations of seizures leaving unaffected their electrographic pattern. The effects of GVG and GAG are attributed in part to decreased arousal. Practical implications of these findings are discussed.
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PMID:Effects of gamma-acetylenic GABA and gamma-vinyl GABA on metrazol-activated, and kindled seizures. 50 7

The GABA withdrawal syndrome (GWS) is a new model of focal epilepsy in which paroxysmal activity is induced through the interruption of a chronic, intracortical infusion of GABA. Preliminary studies have shown extraordinary resistance of this epileptogenic activity to classic anticonvulsants including diazepam, the most effective agent for treating status epilepticus. However, GWS can be inhibited by GABA itself. The rat with petit mal-like seizures is a genetic model of generalized non-convulsive epilepsy (GNCE), with behavioral characteristics and electrical (spike-and-wave discharges) signs resembling absences. Moreover, GABAmimetics aggravate this type of seizure. Rats with GWS induced by cessation of a localized GABA infusion (50 micrograms/microliters/h for 24 h), and the rat model of GNCE, were treated with HEPP, a new anticonvulsant agent. In the case of GWS, the drug produced a significant decrease of focal spike activity in animals which started discharging at low frequencies while in rats with higher frequency discharge, HEPP was without effect. HEPP administered on the second day of the GWS in naive rats had no effect. In rats with GNCE, doses of 50 and 100 mg/kg i.p. blocked the spike-and-wave discharges. The higher dose produced sedation in this absence seizures model. Although the mechanism of action of HEPP is still unknown, its unique antiepileptic profile deserves further studies.
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PMID:Effects of 3-hydroxy,3-ethyl,3-phenylpropionamide (HEPP) on rat models of generalized and focal epilepsy. 139 31

Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. The GABA content was measured 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. In other groups of rats seizures were elicited by i.p. injection of (+)-bicuculline (3 mg/kg) 24 hours, 48 hours, 4 days, 14 days and 3 months after BCCA. Analysis of the GABA content revealed significant increase compared with controls in the hippocampus, frontal cortex and substantia nigra from 24 hours up to 3 months. Bicuculline treatment induced tonic/clonic seizures and status epilepticus in sham operated animals; these effects were drastically diminished at various time points after BCCA. The present results suggest that BCCA produces a longlasting increase in GABA content and as a consequence protection from bicuculline-induced seizures.
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PMID:Transient reduction of cerebral blood flow leads to longlasting increase in GABA content in vulnerable structures and decreased susceptibility to bicuculline induced seizures. 163 44

The relationship between an episode of status epilepticus, the resulting hippocampal pathology, and the subsequent development of pathophysiological changes possibly relevant to human epilepsy was explored using the experimental epilepsy model of perforant path stimulation in the rat. Granule cell hyperexcitability and decreased feedforward and feedback inhibition were evident immediately after 24 hours of intermittent perforant path stimulation and persisted relatively unchanged for more than 1 year. All of the pathophysiological changes induced by perforant path stimulation were replicated in normal animals by a subconvulsive dose of bicuculline, suggesting that the permanent "epileptiform" abnormalities produced by sustained perforant path stimulation may be due to decreased GABA-mediated inhibition. Granule cell pathophysiology was seen only in animals that exhibited a loss of adjacent dentate hilar mossy cells and hilar somatostatin/neuropeptide Y-immunoreactive neurons. GABA-immunoreactive dentate basket cells survived despite the extensive loss of adjacent hilar neurons. However, parvalbumin immunoreactivity, present normally in a subpopulation of GABA-immunoreactive dentate basket cells, was absent on the stimulated side. Whether this represents decreased parvalbumin synthesis in surviving basket cells or a loss of a specific subset of inhibitory cells is unclear. Hyperexcitability and decreased paired-pulse inhibition in response to ipsilateral perforant path stimulation were also present in the CA1 pyramidal cell layer on the previously stimulated side, despite minimal damage to CA1 pyramidal cells or interneurons. The possibility that CA1 inhibitory neurons were hypofunctional or "dormant" due to a loss of excitatory input to inhibitory cells from damaged CA3 pyramidal cells was tested by stimulating the contralateral perforant path in order to activate the same CA1 basket cells via different inputs. Contralateral stimulation evoked CA1 pyramidal cell paired-pulse inhibition immediately in the previously stimulated hippocampus. Thus, we propose the "dormant basket cell" hypothesis, which implies that despite malfunction, inhibitory systems remain intact in "epileptic" tissue and are capable of functioning if appropriately activated.
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PMID:Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. 168 84

In order to test the GABA hypothesis of kindling, GABA-complex antagonists were administered in a dose-response paradigm to rats that had been implanted with indwelling forebrain electrodes, but not kindled. Focal seizures were then elicited from either the cortex or the amygdala to see whether kindling-like secondary generalization would occur. Norharmane, a benzodiazepine inverse agonist, failed to promote secondary generalization from either the cortex or the amygdala. Bicuculline, a GABAA receptor antagonist, and picrotoxin, a chloride ionophore antagonist, enhanced generalization from both sites and, in amygdala-implanted subjects, appeared to produce a significant acceleration of kindling as well. Aminophylline, an adenosine antagonist tested for purposes of comparison, also enhanced secondary generalization from both sites, and in amygdala-implanted subjects produced long electrographic discharges which sometimes developed into status epilepticus.
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PMID:Secondary generalization in non-kindled rats following acute administration of GABA-complex and adenosine antagonists. 169 79

Rats were exposed for 24 min to bilateral clamping of the common carotid arteries (BCCA) in pentobarbital anaesthesia. 14 days later the animals were subjected to subcutaneous injection of (+)-bicuculline (3 or 4 mg/kg). A significantly decreased susceptibility to bicuculline-induced seizures could be observed in BCCA treated rats compared with sham operated controls. It is suggested that BCCA treatment protects animals against status epilepticus and lethal toxicity produced by bicuculline. Electrographic recordings of the BCCA animals revealed no ictal activity within 1 h after bicuculline injection. An analysis of the GABA content showed a significant increase in the hippocampus (HPC), frontal cortex (FCX), parietal cortex and substantia nigra in BCCA animals compared with controls. It is therefore possible that an increase in GABA content postsynaptically counteracts the GABAA antagonistic effect of bicuculline in BCCA animals thus preventing the normal seizure inducing effect of this substance.
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PMID:Decreased susceptibility to seizures induced by bicuculline after transient bilateral clamping of the carotid arteries in rats. 185 Feb 83

The spatial and temporal EEG features of the epileptogenic syndrome induced by cessation of chronic intracortical GABA infusion in normal rats are described. In the initial stages, the paroxysmal discharges (PDs) induced by withdrawal from unilateral GABA application may appear either unilaterally or bilaterally, although with greater amplitude on the infused side. PDs are transitorily accompanied by behavioral signs of distal myoclonus of the body territory corresponding to the infused area (contralateral hindlimb). Later, the paroxysmal activity becomes more localized, circumscribed to the cannula-infused site and with ipsilateral propagation to anterior cortical areas. The amplitude of PDs decreases progressively while their frequency increases, reaching its maximal value at about 4 h after the first PDs have appeared. In the final stages of the syndrome, which may last several days, clinical manifestations are absent and PDs are activated by slow-wave sleep and reduced during REM sleep and waking. Chronic intracortical applications of taurine failed to induce any electroclinical changes on withdrawal and were unable to inhibit the focus elicited by GABA withdrawal, whereas reinstatement of GABA infusion into the epileptogenic area was effective in blocking the paroxysmal activity. Intracortical infusion of baclofen induced the appearance of an epileptogenic focus that waned on withdrawal. The GABA-withdrawal syndrome appears to be a new model of focal status epilepticus; it may be useful as an experimental model of human partial epilepsy to investigate the role of GABAergic neurotransmission.
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PMID:Electroencephalographic study of the GABA-withdrawal syndrome in rats. 236 74

A period of continuous hippocampal stimulation (CHS) establishes an acute condition of self-sustaining limbic status epilepticus (SSLSE) which is followed by chronic neuropathological changes reminiscent of hippocampal sclerosis encountered in epileptic patients. In the chronic (greater than or equal to 1 month) condition following CHS-induced SSLSE, extended electrographic monitoring in the hippocampus revealed spontaneous recurrent paroxysmal discharges. All 6 animals studied had persistent interictal spiking; 3 had multiple fully developed electrographic seizures. There was a marked diminution of paired pulse inhibition, demonstrated by a protocol known to reflect the potency of inhibition mediated by GABAA receptors. Hippocampal slices from animals that had previously experienced CHS-induced SSLSE demonstrated an increased excitability relative to slices from control animals as evidenced by epileptiform bursting in increased extracellular potassium ([K+]0) and decreased extracellular calcium ([Ca2+]0). These studies establish that CHS-induced SSLSE in rats provides an experimental model with recurrent spontaneous hippocampal seizures. Based on electrophysiological data we suggest that a decrease in GABA-mediated inhibition and/or altered sensitivity to extracellular ions may play roles in the development of such seizures.
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PMID:Recurrent spontaneous hippocampal seizures in the rat as a chronic sequela to limbic status epilepticus. 238 85

Subconvulsant doses (20 mg/kg) of pilocarpine administered to a kindled rat convert a kindled seizure to status epilepticus. The hippocampus is involved in such status epilepticus. Furthermore, evidence is accumulating that GABA-mediated inhibition in the hippocampus is chronically diminished by kindling. The studies presented here compared the electrophysiologic effects of pilocarpine in vivo in the CA1 region of the hippocampus in naive and amygdala-kindled rats. A paired pulse paradigm previously shown to quantify the potency of GABAergic inhibition was employed. Stimuli were delivered in the CA3 region of urethane-anesthetized rats and population spikes were recorded in the contralateral CA1 region. In naive rats, pilocarpine (6-60 mg/kg) caused a left shift in the input-output curve measuring stimulus intensity vs population spike amplitudes, indicating an increase in neuronal excitability. In addition, paired pulse inhibition was reduced for interpulse intervals less than 70 ms. In amygdala-kindled rats, neuronal excitability was also enhanced following pilocarpine administration. The potency of baseline paired pulse inhibition was decreased in kindled rats compared to naive controls. Following pilocarpine, inhibition for interpulse intervals less than 70 ms was further reduced, but to a lesser extent than in naive rats. These findings suggest that the ability of subconvulsive doses of pilocarpine to change a discrete kindled seizure triggered by one stimulus to status epilepticus depends on the suppression of GABAergic inhibition below a critical level.
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PMID:Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats. 272 29

Positron emission tomography (PET) was used to investigate, in the living baboon, the in vivo modulation of [11C]Ro 15-1788 binding to benzodiazepine receptors in brain and the changes with ligands acting at the supramolecular complex during status epilepticus induced by pentylenetetrazole. The central type benzodiazepine receptors were labelled in vivo by intravenous injection of [11C]Ro 15-1788. Simultaneous positron emission tomography and electroencephalographic activity recording evidenced a modulation of the brain binding of [11C]Ro 15-1788 during pentylenetetrazole-induced status epilepticus. We investigated the changes in the modulation of radioligand kinetics and in seizure activity after intravenous administration of a benzodiazepine agonist (diazepam, 1.5 mg/kg), a benzodiazepine antagonist (Ro 15-1788, 2 mg/kg), a GABA agonist (progabide, 50 mg/kg) and a ligand of the picrotoxin/barbiturate binding sites (LY81067, 3.5 mg/kg). The results showed that there is an in vivo competitive interaction of pentylenetetrazole with the benzodiazepine receptors, as reflected by the low displacement of [11C]Ro 15-1788 in the first 10 min of the status epilepticus. However, in contrast to diazepam, progabide and LY81067, a dose (2 mg/kg) of Ro 15-1788 that saturates the benzodiazepine receptors was unable to block the seizures induced by pentylenetetrazole. This indicates that the benzodiazepine receptors play only a minor role in the status epilepticus induced by pentylenetetrazole. The contribution of other binding sites within the supramolecular complex is assessed.
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PMID:Status epilepticus induced by pentylenetetrazole modulates in vivo [11C]Ro 15-1788 binding to benzodiazepine receptors. Effects of ligands acting at the supramolecular receptor complex. 283 6


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