Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Using the immature (8-12 days postnatal) rabbit hippocampal slice preparation, we investigated regional extracellular potassium concentration [( K+]o) changes that occur during spontaneous and evoked spreading depression (SD) episodes. We report here a difference between the CA1 and CA3 cell populations in the immature hippocampus with regard to 1) resting [K+]o, 2) magnitude of the [K+]o change during seizurelike events and SDs, and 3) susceptibility to SD episodes. Experiments were also performed to elucidate the roles that the Na-K pump and synaptic inhibition play in controlling SD onset, duration, and recovery. We demonstrated a major role for potassium regulation by the Na-K pump and a lesser modulatory role for inhibitory postsynaptic potentials (IPSPs) in preventing SD in the CA3 region. 2. Simultaneous intra- and extracellular recordings were made in the CA1 and CA3 regions of the immature rabbit hippocampus during spontaneous or evoked SD, while potassium ion-sensitive microelectrodes (K-ISMs) monitored changes in [K+]o. The CA1 region had 1) a higher frequency of spontaneous SD episodes than CA3, 2) a lower threshold to potassium-triggered SD, 3) a longer duration SD episode, and 4) smaller post-SD membrane potential and [K+]o undershoots (below the original resting membrane potential and resting [K+]o). 3. During the onset of a SD episode in the CA1 region, the local [K+]o rose either before or at the same time as the membrane potential depolarization. 4. In the CA3 region, spontaneous ictallike events consisting of tonic cell depolarization with repetitive activity followed by clonic afterdischarges were more likely to occur than SD episodes. During these ictallike episodes, [K+]o rose above the 10- to 12-mM ceiling level reported for adult CNS tissue during seizures. Increases in [K+]o evoked by repetitive stimulation were regulated at a lower level in CA3 (average [K+]o rise to 11.4 mM) than in CA1 (average [K+]o rise to 18.3 mM). 5. In CA3, bath application of 10 microM bicuculline or 3.4 mM penicillin did not change the frequency of spontaneously occurring SDs or the SD response threshold to local pressure ejection of 2 M KCl. However, blockade of IPSPs did lead to lower thresholds for SD or seizurelike episodes elicited by stimulation of the mossy fibers. 6. A single application of ouabain (10 microM) to CA3 by local pressure ejection caused a slow rise in local [K+]o measured with K-ISMs. The ouabain treatment also increased the frequency of spontaneous postsynaptic potential activity and decreased the amplitude and duration of CA3 pyramidal cell afterhyperpolarizations (AHPs).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of Na-K pump potassium regulation and IPSPs in seizures and spreading depression in immature rabbit hippocampal slices. 231 42

We have developed a model of cyclosporin A (CsA) central nervous system toxicity in the Munich-Wistar rat in which CsA, 20 mg/kg/day i.p., produces significant EEG abnormalities and mortality. In the present study we used cohorts of Munich-Wistar rats to assess effects of CsA on the threshold for tonic-clonic electroshock-induced seizures. Rat cohorts were begun on cremephore, CsA-10 mg/kg/day, or CsA-20 mg/kg/day. On day 7 and day 14 of the dosing protocol, cohorts of animals were exposed to maximal electroshock (MES) using a minimal staircase method within each cohort. Multiple logistic regression models were used to determine differences between groups on the relative odds of producing a MES-induced seizure while controlling for other variables. Seizure threshold was significantly affected by shock amperage and body weight, but not by SUN, creatinine, bilirubin, sodium, potassium, weight loss or day the shock was delivered. The odds ratios of seizure induction in the CsA-treated groups versus placebo group were 1.91 for CsA-10 mg/kg/day and 3.63 for CsA 20-mg/kg/d, both statistically significant. These results suggest that cyclosporine lowers seizure threshold and probably increases susceptibility to seizures, the etiology of which may be multifactorial clinically.
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PMID:Cyclosporine lowers seizure threshold in an experimental model of electroshock-induced seizures in Munich-Wistar rats. 232 2

The release of endogenous amino acids from hippocampal CA1 subslices under basal conditions and the release evoked by high potassium (50 mM K+) depolarization was studied during kindling epileptogenesis. Emphasis was put on the release of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate. Kindling was induced by tetanic stimulation of the Schaffer-collaterals/commissural fibers of the dorsal hippocampus of the rat. The calcium-dependent GABA release in the presence of high K+ was significantly increased (40-46%) in fully kindled animals, 24 h after the last seizure, in comparison to controls. At long-term, 28 days after the last seizure, the calcium-dependent GABA release was still significantly increased (45-49%). An increased release of GABA in kindled animals was still found when GABA uptake was blocked by nipecotic acid. In contrast, no significant alterations were encountered in the basal or high potassium induced release of the excitatory amino acids aspartate and glutamate. These results suggest that kindling epileptogenesis is accompanied by a specific and long-lasting enhancement of GABA exocytosis which may lead to a desensitization of the GABA receptor, and thus determine the increase of seizure sensitivity.
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PMID:Kindling increases the K(+)-evoked Ca2(+)-dependent release of endogenous GABA in area CA1 of rat hippocampus. 233 17

Ten patients with multiple sclerosis (MS) were enrolled in a preliminary trial of the potassium channel blocker, 3,4-diaminopyridine, to evaluate drug toxicity and pharmacokinetics. The patients were treated with oral 3,4-diaminopyridine, first with increasing single doses up to 100 mg and then with divided dosage for up to 3 weeks. Paresthesias were reported by all patients and abdominal pain was dose limiting in 6 patients. 3,4-Diaminopyridine levels and half-life varied widely from patient to patient. Cerebrospinal fluid levels of 3,4-diaminopyridine were about 10% of those in serum. Neither seizures nor epileptiform changes on electroencephalographic examination occurred. Small reversible improvements in specific neurological deficits were seen on examination in all patients and reversible improvement in visual evoked response latencies were found in 2 patients. These results suggest that further study of 3,4-diaminopyridine in patients with MS is warranted.
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PMID:Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis. 235 97

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

A 23-year-old man survived a suicide attempt in which he had swallowed 1500 mg potassium cyanide. Initially there were cerebral seizure and marked lactacidosis. Six hours after hospital admission the cyanide blood level was 6 mg/l. The poisoning having at first not been recognized he at that time merely received supportive treatment to counteract the acidosis, as well as assisted ventilation with hyperventilation and hyperoxigenation. Afterwards, sodium thiosulphate was given additionally for 24 h at a dosage of 1 g per hour. The clinical course underlines the great importance of supportive measures in the treatment of cyanide poisoning. In the individual case the balance between risk and value of an intrinsically toxic antidote administration must be critically assessed.
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PMID:[Cyanide poisoning: treatment with hyperoxygenation and sodium thiosulphate]. 237 41

The factors responsible for the unusual susceptibility of the hippocampus to seizures and ischemic cell damage are not well understood. The CA1 pyramidal subfield of the hippocampus is particularly vulnerable to seizure activity and damage after ischemia. The possibility was examined that regional differences exist in extracellular volume, which might influence neuronal excitability and response to injury in the hippocampus. CA1 stratum pyramidale exhibited an exceptionally low extracellular volume fraction (EVF) of 0.12, whereas the EVFs of CA3 and dentate were considerably higher--0.18 and 0.15, respectively. The EVF of CA1 stratum pyramidale was reversibly reduced by 30 percent when the extracellular potassium concentration was raised from 3.5 to 8.5 mM, a procedure that induced spontaneous electrographic seizures in CA1. Thus there are regional variations in the properties of the extracellular space in the hippocampus that might underlie the propensity of the CA1 region to develop seizures and to suffer damage after ischemia.
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PMID:Regional variation of extracellular space in the hippocampus. 238 42

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

It has been known that various derangements in ionic homeostasis develop following neural trauma. In particular, potassium efflux out of and calcium influx into the cells are thought to play important roles in causing cell damage. Concomitantly we have previously reported that increased extracellular potassium per se provoked by head injury induces convulsive seizure such that the sustained high extracellular potassium leads to animal death. The purpose of the present study was further to examine the beneficial effect of drugs which could inhibit such detrimental ion movements in experimental head injury. Awake male mice of dd-strain were restrained and subjected to head injury using a bakelite weight of 30 gm dropped from a height of 17.6 cm above the skull. This injury resulted in immediate loss of consciousness in 100%, convulsive seizure in about 70% and death in about 30% of animals. The severity of consciousness disturbance was evaluated by a pair of indices in time interval; time required for the recovery of righting reflex (RR) and for the recovery of spontaneous movement (SM). Ethacrynic acid, a loop diuretics, blocks carrier-mediated chloride transport into astroglia associated with sodium and water in the presence of high extracellular potassium. Animals were treated with either 0.5-1.0 mg/kg or 2.0-4.0 mg/kg of ethacrynic acid administered via tail vein 10 min before injury. In the other group of animals, a calcium entry blocker, flunarizine was injected intraperitoneally in doses 5, 10 and 20 mg/kg one hour pre-insult.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Protective effect on the brain of ion-blockers in experimental head injury]. 243 80

Penicillin is well known as a potent convulsive agent. A cortical topical, intracerebral or systemic administration of penicillin produces abnormal and paroxysmal activity which may lead to seizure, and has been used in the investigation of the mechanisms of epilepsy. This is a report on the studies of an acute effect of potassium penicillin G on two models of experimental focal epilepsy: a) amygdaloid kindling model, and b) kainic acid-induced limbic seizure model. Twelve adult cats for amygdaloid kindling model (kindling group), six for KA-induced limbic seizure model (KA group) and four for a control group were prepared for this study. In kindling group, after completion of kindling procedure, 40-60 X 10(4) unit/kg of potassium penicillin G (PC), dissolved in sterilized normal saline, was injected intraperitoneally during an interictal period. In KA group, 1 micrograms of KA was injected into the left amygdala. Limbic seizures occurred frequently during the initial 5 hours but subsided completely within 3 days. After a latent period, spontaneous secondarily generalized convulsion occurred from 30 to 60 days after KA injection. The cats were completely normal in their behavior during the interictal period. During the interictal stage after the first generalized convulsion has been observed, 15-20 X 10(4) unit/kg of PC was injected intraperitoneally. In the control group, 40-60 X 10(4) unit/kg was injected intraperitoneally. Electroclinical observations were continued until 5 hours after PC injection in three groups. In the control group, no cats developed generalized convulsion. In the kindling group, 4 of 12 cats developed focal amygdaloid seizures with secondary generalization by nearly the identical doses required in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Acute effect of penicillin G on feline models of focal epilepsy]. 250 15


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