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)

Ruthenium red was administered to mice and cats intracranially or intraperitoneally. In mice, intracisternal administration produced status epilepticus and tonic convulsions. In contrast, intraperitoneal administration induced total flaccid paralysis lasting several hours. These effects of Ruthenium red were partially blocked by the simultaneous administration of CaCl2. EDTA, at doses much greater than those of Ruthenium red, produced effects similar to those of the dye, which were also blocked by CaCl2 administration. In cats, intraventricular or intrahippocampal administration of Ruthenium red through a permanently implanted cannula produced after a few minutes subclinical paroxysmal activity in all brain regions recorded. After several hours the animals developed typical grand mal seizures. Intraperitoneal injection of Ruthenium red to cats did not affect the EEG but markedly depressed muscular activity. Administration of carbachol to the latter animals produced myoclonic responses. These results are discussed in relation to the inhibitory effect of Ruthenium red on Ca2+ transport and binding to membranes, and to the role of this cation on neurotransmitter release.
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PMID:Convulsions or flaccid paralysis induced by ruthenium red depending on route of administration. 82 18

Understanding the molecular basis of altered neuronal excitability in epilepsy is a major challenge in neuroscience research. The present study suggests an inverse correlation between changes in neuronal excitability in status epilepticus and the activity of type II multifunctional calcium/calmodulin-dependent kinase II (CaM kinase II), a major Ca(2+)-signal transducing system in brain. 'Continuous' hippocampal stimulation (CHS), a new model of non-convulsive limbic status epilepticus (SE), mimics the progression of electrographic changes characteristic in human SE and allows for quantitation of post-stimulus seizure severity. In the present study, hippocampus and anterior neocortex from CHS-stimulated rats and paired surgical controls were assayed for CaM kinase II activity by incorporation of radiolabeled phosphate from [gamma-32P]ATP into the 50-kDa subunit of the kinase itself (autophosphorylation). In all instances, CHS induced sustained interictal bursting and/or electrographic seizures. Decreased CaM kinase II activity was seen in all preparations from electrically stimulated hippocampus. CaM kinase II activity in CHS animals was diminished by 37% relative to controls (P less than 0.01; Student's paired t-test). The progressive intensity of the EEG discharges correlated directly with the decrement of CaM kinase II activity (P less than 0.05; Spearman's rank correlation test, n = 5). This is the first report of a dynamic modulation of a biochemical system that has been implicated in neuronal excitability in coordination with the characterized developmental stages of SE.
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PMID:Loss of type II calcium/calmodulin-dependent kinase activity correlates with stages of development of electrographic seizures in status epilepticus in rat. 131 99

The pattern of hippocampal cell death has been studied following hippocampal seizure activity and status epilepticus induced by 110-min stimulation of the perforant pathway in awake rats. The order of vulnerability of principal cells in the different hippocampal subfields--as determined by silver impregnation--was found to be very similar to the pattern found in ischemia; i.e., dentate hilus greater than CA1, subiculum greater than CA3c greater than CA3a,b greater than dentate granule cells. The hilar somatostatin-containing cells were the most vulnerable cell type, whereas all other subpopulations of nonprincipal neurons--visualized by immunocytochemistry for the calcium binding proteins parvalbumin and calbindin--were remarkably resistant. Pyramidal cells in the CA3 region containing neither of the examined calcium binding proteins were more resistant to overexcitation than CA1 pyramidal cells, most of which do contain calbindin. This indicates that no simple relationship exists between vulnerability in status epilepticus and neuronal calcium binding protein content, and that local and/or systemic hypoxia during status epilepticus may be responsible for the ischemic pattern of cell death.
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PMID:Pattern of neuronal death in the rat hippocampus after status epilepticus. Relationship to calcium binding protein content and ischemic vulnerability. 134 49

In conscious rats, continuous i.v. infusion of cocaine (2 mg/kg/min) produced a marked increase in blood pressure, an initial moderate increase followed by a decrease in heart rate, tonic-clonic convulsions and, finally, a lethal episode of status epilepticus. No change in rectal temperature was observed. Infusion of cocaine methiodide (2 mg/kg/min), a quaternary derivative of cocaine, also produced a lethal episode of status epilepticus, but it was 6 times less potent than cocaine on a molar basis. In pentobarbital-anesthetized, spontaneously breathing rats, cocaine produced death by respiratory failure. Artificial ventilation of pentobarbital-anesthetized rats elevated the lethal dose of cocaine by 15-fold and these animals died of marked hypotension. In conscious rats, pretreatment with dl-, d- or l-propranolol or the alpha 2-selective adrenoceptor antagonist yohimbine enhanced the convulsive and lethal effects of cocaine. In contrast, the alpha 2-selective adrenoceptor agonist clonidine or the alpha 1-selective adrenoceptor antagonist prazosin attenuated these effects. Yohimbine antagonized the protective effect of clonidine. The nonselective alpha adrenoceptor antagonist phentolamine, the autonomic ganglionic blocker chlorisondamine and various calcium channel blockers had no effect on the convulsive or lethal doses of cocaine. The pressor response to cocaine was attenuated by calcium channel blockers, clonidine, phentolamine and dl- or l-propranolol, but not by d-propranolol. The pressor response to cocaine was abolished by chlorisondamine, reversed to a depressor response by prazosin and enhanced by yohimbine. The initial tachycardiac response to cocaine was reversed to bradycardia by dl- and l-propranolol, prazosin, yohimbine or high doses of the calcium channel blockers, but was unaffected by phentolamine, d-propranolol, clonidine or chlorisondamine. These results indicate that in spontaneously breathing animals, acute i.v. infusions of lethal doses of cocaine produce death primarily by central effects, namely by status epilepticus in conscious rats and by respiratory arrest in pentobarbital-anesthetized rats. In artificially ventilated, pentobarbital-anesthetized rats, however, cocaine produces death by effects on the cardiovascular system. In conscious rats, endogenous alpha 1 adrenoceptors exert a deleterious influence on cocaine-induced convulsive and lethal effects, whereas alpha 2 adrenoceptors provide protective influence. Propranolol appears to enhance cocaine-induced acute lethality through a mechanism independent of beta adrenoceptors. Calcium channel blockers appear ineffective in antagonizing cocaine's lethality.
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PMID:Pathophysiological and pharmacological mechanisms of acute cocaine toxicity in conscious rats. 152 34

Seizures induced by three convulsant treatments produced differential effects on the concentration of acetylcholine in rat brain. Status epilepticus induced by (i) coadministration of lithium and pilocarpine caused massive increases in the concentration of acetylcholine in the cerebral cortex and hippocampus, (ii) a high dose of pilocarpine did not cause an increase of acetylcholine, and (iii) kainate increased acetylcholine, but the magnitude was lower than with the lithium/pilocarpine model. The finding that the acetylcholine concentration increases in two models of status epilepticus in the cortex and hippocampus is in direct contrast with many in vitro reports in which excessive stimulation causes depletion of acetylcholine. The concentration of choline increased during seizures with all three models. This is likely to be due to calcium- and agonist-induced activation of phospholipase C and/or D activity causing cleavage of choline-containing lipids. The excessive acetylcholine present during status epilepticus induced by lithium and pilocarpine was responsive to pharmacological manipulation. Atropine tended to decrease acetylcholine, similar to its effects in controls. The N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801, reduced the excessive concentration of acetylcholine, especially in the cortex. Inhibition of choline uptake by hemicholinium-3 (HC-3) administered icv reduced the acetylcholine concentration in controls and when given to rats during status epilepticus. These results demonstrate that the rat brain concentrations of acetylcholine and choline can increase during status epilepticus. The accumulated acetylcholine was not in a static, inactive compartment, but was actively turning-over and was responsive to drug treatments. Excessive concentrations of acetylcholine and/or choline may play a role in seizure maintenance and in the neuronal damage and lethality associated with status epilepticus.
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PMID:Seizures increase acetylcholine and choline concentrations in rat brain regions. 181 38

The use of magnesium sulfate (MgSO4) as an anticonvulsant is controversial. Status epilepticus was induced in 0.5% halothane-anesthetized Wistar rats with a threshold (90 mg/kg) or suprathreshold (200 mg/kg) dose of intravenous (i.v.) pentylenetetrazol (PTZ) under stereotactic hippocampal depth electrode monitoring. Fifteen minutes after seizure induction, the maximum hemodynamically tolerated dose of MgSO4 (10 mg/kg/min in 22 min) was administered i.v. MgSO4 was ineffective in altering seizure discharge. A subgroup of nine animals received hypertonic mannitol before MgSO4 to open the blood-brain barrier (BBB) to facilitate Mg2+ CNS penetration. Again MgSO4 was ineffective in attenuating epileptic activity. These results support the contention that MgSO4 is not an effective treatment for status epilepticus. We hypothesize that because Mg2+ blocks Ca2+ influx into the neuron through the N-methyl-D-aspartate (NMDA) receptor-operated calcium channel in a voltage-dependent manner it would be ineffective in neurons that are continuously depolarizing as in status epilepticus.
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PMID:Effects of magnesium sulfate on pentylenetetrazol-induced status epilepticus. 183 Nov 20

Status epilepticus (SE) remains one of the most serious disorders affecting the central nervous system. Recent progress in understanding the mechanisms of the brain damage produced by SE make even more apparent the need to quickly terminate this condition, prevent its recurrence, and treat its complications. Intracellular calcium concentrations rise, prompting a cascade of excitotoxic consequences. Therapy for SE currently consists of agents which stop seizures (benzodiazepines, phenytoin, barbiturates). This review discusses their use in SE.
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PMID:Convulsive disorders: status epilepticus. 207 Mar 61

The behavioral and electrographic effects of 4-aminopyridine (4-AP) administered i.p. or microinjected into the hippocampal CA1 region (i.h.) were studied in rats. The modification of such effects by the systemic administration of the Ca2+ antagonist dihydropyridine, nifedipine, was also studied. 4-AP i.p. (5 mg/kg) induced generalized tonic convulsions in 74% of the animals and death in 13%. Convulsions were characterized by electrical discharges of relatively short duration in all structures studied (frontal cortex, amygdala, dorsal hippocampus and dorsal raphe). Limbic seizures and frequent wet-dog shakes were observed when 4-AP was administered i.h. (2-4 nmol) and this behavior was correlated with hippocampal discharges, which rapidly propagated to the other structures. Pretreatment with nifedipine (7.5-50 mg/kg s.c.) markedly potentiated the effects of 4-AP. The percentage of rats that died during generalized convulsion after i.p. 4-AP increased to 56-87% and the frequency of wet-dog shakes increased after i.h. microinjection of 4-AP. Moreover, nifedipine-treated rats showed long-lasting (greater than 60 min) continuous discharges in all structures studied (status epilepticus). These results are discussed in the light of the possible participation of Ca2+ channels in the convulsant effect of 4-AP and its potentiation by nifedipine.
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PMID:Seizures and wet-dog shakes induced by 4-aminopyridine, and their potentiation by nifedipine. 234 Aug 61

Status epilepticus of sufficient duration (greater than 30 min) causes a unique lesion of substantia nigra pars reticulata (SNPR), and of globus pallidus (GP). This lesion, which encompasses a pan-necrotic destruction of neurons and glial cells seems to develop during ongoing seizures. We decided to investigate if the lesion is accompanied by net calcium accumulation. Seizures of 20 and 60 min duration were induced by the administration of flurothyl, and the tissue was frozen in situ either at the end of the seizure periods, or after recovery periods of 15 or 120 min. The total calcium and potassium contents of caudoputamen, neocortex, GP and SNPR were measured using particle induced X-ray emission (PIXE) in the microprobe mode. Seizures of 20 min duration did not cause net accumulation of calcium. When the duration of seizures was extended to 60 min the results varied depending on the location. In caudoputamen, which does not incur neuronal damage, no calcium accumulation was observed. In GP and SNPR, such a rise was unequivocally demonstrated, with calcium content increasing to about 150% of controls. The increase in calcium correlated to a decrease in potassium content. It is concluded that epileptic cell death occurs pari passu with accumulation of calcium although it cannot be stated that this accumulation is the cause of the cell death. It is speculated that seizures increase the permeability of the blood-brain barrier to calcium, and that enhanced blood to tissue transfer increases the calcium load of metabolically strained cells.
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PMID:Accumulation of calcium in substantia nigra lesions induced by status epilepticus. A microprobe analysis. 235 29

The effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced seizures were studied in 30 0.5% halothane anesthetized Sprague-Dawley rats. Each animal received low dose kainic acid 0.5 mg/kg i.v. to allow study of the progression of neuronal excitability and epileptiform activity. Preadministration of nimodipine 1.0 mg/kg i.p. increased the latency but did not prevent kainic acid-induced epileptic activity. For example, the latency from kainic acid administration to the appearance of the first seizure and status epilepticus was 75.6 +/- 9.1 min and 85.9 +/- 9.4 min in controls vs. 117.3 +/- 9.3 min and 128.0 +/- 8.7 min in the nimodipine group (P less than 0.005). It is hypothesized that nimodipine attenuated excitability by blocking Ca2+ influx through voltage-dependent L-channels secondary to kainic acid-induced membrane depolarization.
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PMID:Effects of the dihydropyridine Ca2+ channel antagonist nimodipine on kainic acid-induced limbic seizures. 235 53


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