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

We investigated the efficacy of focal perfusion of diazepam (DZP) in reducing seizures produced by focal cobalt and systemic pilocarpine in the rat. Cobalt chloride crystals (3.5 mg/kg) were inserted stereotactically into the left hippocampus and recording electrodes affixed to the head of 23 rats. Focal spiking was evident within 5-7 days of implantation. Occasional ictal electrographic events were observed with cobalt alone, but consistent ictal events could be produced by intraperitoneal injection of pilocarpine hydrochloride (60 mg/kg) into the cobalt-treated animals. When rhythmical spiking was observed, the animals were treated either with DZP (0.25 mg in 50 microliters) or a vehicle (VEH) delivered into the left hippocampus. Blinded spike counts before and after injection showed spiking at 133.3 +/- 53.4% of baseline (mean +/- SD, n = 8) for the VEH-treated animals and 2.7 +/- 3.3% (n = 8) for the DZP-treated animals. Ictal events occurred in seven of the eight VEH-treated and two of the eight DZP-treated rats. Mean time to the first ictal event was 5.9 +/- 6.9 min for VEH-treated animals and 24 +/- 32.6 min for DZP-treated animals. DZP injected into the hippocampus contralateral to the cobalt did not reduce spiking. Systemic levels of DZP were unmeasurable in nine of ten tested animals. Focal perfusion of DZP therefore effectively reduced spiking in this cobalt chloride/pilocarpine model of focal and secondarily generalized epilepsy. This model, while involving GABAergic mechanisms, does not entirely depend upon GABAergic mechanisms. The findings therefore broaden the possibility of using focal DZP as a treatment for partial seizures.
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PMID:Interictal and ictal activity in the rat cobalt/pilocarpine model of epilepsy decreased by local perfusion of diazepam. 941 56

The authors report two cases of ischemic stroke secondary to occlusive vasculopathy two decades after radiation therapy (RT) for medulloblastoma. Both patients underwent posterior fossa medulloblastoma partial resection, followed by craniospinal RT in which a cobalt 60 source was used; 40 Gy were given to the whole brain plus a 15-Gy boost to the posterior fossa. Both patients received multiagent chemotherapy, immediately following radiation therapy in the first case and after repeated craniotomy for recurrence 13 years after radiation in the second case. They experienced multiple sequelae from radiation and chemotherapy, including growth retardation and psychomotor delay. However, 20 years after treatment, they remained tumor free and able to work, until they presented with focal neurological deficits and seizures. Computerized tomography and magnetic resonance imaging of the brain in both cases showed no tumor recurrence, but did demonstrate ischemia in a posterior cerebral artery distribution. Cerebral angiography revealed multiple mid-sized arterial wall irregularities as well as focal stenoses consistent with a postirradiation vasculopathy. The pathophysiological mechanisms, radiological appearance, and incidence of this syndrome are reviewed from the literature.
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PMID:Late postirradiation occlusive vasculopathy in childhood medulloblastoma. Report of two cases. 972 22

Tumor and normal tissue response was assessed in 21 dogs with malignant nasal tumors given 42 Gy cobalt radiation in 9 or 10 fractions over 11 to 13 days. Local tumor/clinical relapse recurred in 68% of dogs, with a median relapse free interval (RFI) of 270 days. Median survival was 428 days. One year survival for all dogs was 60%. RFI and survival times are better than, or similar to, previous reports of dogs treated with radiotherapy only. Acute radiation effects were severe in one dog. Late effects were severe in six of 15 dogs (40%) with durable tumor control. Late effects included bilateral blindness (3), osteoradionecrosis (3), and seizures (1). These six dogs had a median survival of 705 days. Loss of vision occurred in at least one eye in nine dogs (47%). Tumor staging based on CT findings was predictive for survival duration. Tumor histology was not predictive of outcome. Labrador Retrievers were significantly over-represented. Despite comparable or improved tumor control and survival times provided by this accelerated protocol, relative to other radiotherapy reports, local failure remains the major cause of death, and late radiation effects can be severe in dogs with durable tumor control.
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PMID:An accelerated technique for irradiation of malignant canine nasal and paranasal sinus tumors. 977 2

We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptide specific to the N-terminus domain of the GluR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GluR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GluR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy.
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PMID:Monitoring of brain spiking activity and autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptors in blood serum of rats with cobalt-induced epilepsy. 979 34

When near-threshold electrical stimulation is used to evoke epileptiform discharges in brain slices, a latent period of up to 150 msec elapses before the discharge begins. During this period most neurons are silent, and abnormal electrical activity is difficult to detect with microelectrodes. A fundamental question about epileptiform activity concerns how synchronous discharges arise abruptly in a relatively quiescent slice. This issue was addressed here by using voltage imaging techniques to study epileptiform discharges in rat piriform cortex slices. These experiments revealed two distinct forms of electrical activity during the latent period. (1) A steeply increasing depolarization, referred to here as onset activity, has been described previously and occurs at the site of discharge onset. (2) A sustained depolarization that precedes onset activity, referred to here as plateau activity, has not been described previously. Plateau and onset activity occurred in different subregions of the endopiriform nucleus (a region of high seizure susceptibility). When cobalt or kynurenic acid was applied focally to inhibit electrical activity at the site of plateau activity, discharges were blocked. However, application of these agents to other nearby sites (except the site of onset) failed to block discharges. Plateau activity represents a novel form of electrical activity that precedes and is necessary for epileptiform discharges. Discharges thus are generated in a sequential process by two spatially distinct neuronal circuits. The first circuit amplifies and sustains activity initiated by the stimulus, and the second generates the actual discharge in response to an excitatory drive from the first.
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PMID:Sustained and accelerating activity at two discrete sites generate epileptiform discharges in slices of piriform cortex. 995 7

A 70-kDa protein, P70, found mostly in the pyramidal cells of the cerebral cortex of cobalt-induced epileptogenic rats, has been implicated in epileptogenesis. The presence of a P70-like substance was searched for immunohistochemically in the cerebral cortex of MGS/ldr, a seizure-sensitive strain of the Mongolian gerbil (Meriones unguiculatus) that we previously established. Immunoreactive aggregates were observed in the pyramidal neurons of the motor cortex and the primary somatosensory cortex. Analysis using confocal laser scanning microscopy revealed that the aggregates were often colocalized with a second type of aggregate with red autofluorescence at the marginal zone of the cell somata. Both aggregates appeared and increased before the appearance of generalized tonic-clonic convulsion. These may be involved in some change of physiological function of the cerebral cortex but their presence itself is not enough to determine the occurrence of epileptic seizure because the gerbils that showed no such seizure had both aggregates.
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PMID:Two types of aggregate in the cerebral cortex of a seizure-sensitive strain of the Mongolian gerbil. 1062 42

The effects of amphetamine on potential changes in both vertebrate and invertebrate central neurons and factors affecting the potential changes were tested. The animals studied included mice, newborn rat and African snail. Seizure was elicited after lethal doses of d-amphetamine (75 mg/kg, i.p.) administration in mice. Repetitive firing of the action potentials were elicited after d-amphetamine (1-30 microM) administration in thin thalamic brain slices of newborn rat. Bursting firing of action potentials in the giant African central RP4 neuron were also elicited after d-amphetamine or l-amphetamine (0.27 mM) administration. The amphetamine elicited bursting firing of action potentials was not blocked even after high concentrations of d-tubocurarine, atropine, haloperidol, hexamethonium administration. Therefore, the amphetamine elicited potential changes may not be directly related to the activation of the receptors of the neuron. The bursting firing of action potentials elicited by amphetamine occurred 20-30 min after amphetamine administration extracellularly, even after high concentrations of d-amphetamine administration (0.27, 1 mM). However, the bursting firing of potentials occurred immediately if amphetamine was administrated intracellularly at lower concentration. Extracellular application of ruthenium red, the calcium antagonist, abolished the amphetamine elicited bursting firing of action potentials. If intracellular injection of EGTA, a calcium ion chelator, or injection with high concentrations of magnesium, the bursting firing of potentials were immediately abolished. These results suggested that the active site of amphetamine may be inside of the neuron and the calcium ion in the neuron played an important role on the bursting of potentials. In two-electrode voltage clamped RP4 neuron, amphetamine, at 0.27 mM, decreased the total inward and steady outward currents of the RP4 neuron. d-Amphetamine also decreased the calcium, Ia and the steady-state outward currents of the RP4 neuron. Besides, amphetamine elicited a negative slope resistance (NSR) if membrane potential was in the range of -50 to -10 mV. The NSR was decreased in cobalt substituted calcium free and sodium free solution. The effects of secondary messengers on the amphetamine elicited potential changes were tested. The bursting firing of action potentials elicited by amphetamine in central snail neurons decreased following extracellular application of H8 (N-(2-methyl-amino) ethyl-3-isoquinoline sulphonamide dihydrochloride), a specific protein kinase A inhibitor and anisomycin, a protein synthesis inhibitor. However, the bursting firing of action potentials were not affected after extracellular application of H7 (1,(5-isoquinolinesulphonyl)-2-methylpiperasine dihydrochloride), a specific protein kinase C (PKC) inhibitor, or intracellular application of GDPbetaS, a G protein inhibitor. The oscillation of membrane potential of the bursting activity was blocked after intracellular injection of 3'-deoxyadenosine, an adenylyl-cyclase inhibitor. These results suggested that the bursting firing of action potentials elicited by d-amphetamine in snail neuron may be associated with the cyclic AMP second messenger system; on the other hand, it may not be associated with the G protein and protein kinase C activity. It is concluded that amphetamine elicited potential changes in both vertebrate and invertebrate central neurons. The changes are closely related to the ionic currents and second messengers of the neurons.
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PMID:Amphetamine elicited potential changes in vertebrate and invertebrate central neurons. 1103 52

The pathogenesis of late-onset epileptic seizures after thrombo-embolic cerebral infarction is poorly understood. Our previous positron emission tomographic (PET) studies with 15O have demonstrated that post-apoplectic epilepsy is associated with more severe brain ischemia, but we were unable to determine if this was the cause or the consequence of the seizures. Using cobalt-55 (55Co) as PET tracer we can now distinguish recurrent, recent infarction in patients with a previous old infarct in the same vascular territory. In seven out of twelve patients with post-apoplectic seizures an increased uptake of 55Co was observed in the border area and in two of them also within the old infarct core. In the control group, composed of eight seizure-free patients with also an old infarct involving the cortical territory of the middle cerebral artery, no increase in 55Co uptake was observed on PET examination. The present study indicates that in a significant number of patients late-onset epilepsy is the clinical expression of recurrent strokes, occurring in the same vascular territory.
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PMID:Cobalt-55 positron emission tomography in late-onset epileptic seizures after thrombo-embolic middle cerebral artery infarction. 1109 6

Epilepsy is one of the most frequently occurring nervous diseases. However, the fundamental cause of epilepsy is still unclear. We tried to elucidate the cellular mechanism of seizure discharge. During this research we unexpectedly found that a herbal mixture prescription shows very good effects on epileptics. Therefore, we also performed experiments on the anticonvulsant mechanism of this herbal mixture prescription, "Saikokeishito-ka-Shakuyaku" (SK). SK showed normalizing effects on intracellular calcium-related and protein-related pathological changes induced by pentylenetetrazol (PTZ) application in snail neurons and cultured neurons from the cerebral cortex of mice. In addition, SK showed marked protective effects against neuron damage induced by the cobalt focus epilepsy model, cytochalasin B and severe stress. SK also showed normalizing effects on developmental defects of cultured neurons from the cerebral cortex of an epilepsy animal model, EL mice. Moreover, SK showed complete preventive effects on the abnormal expression of one of the seizure-related (SEZ) genes, PTZ-17, induced by PTZ in Xenopus oocytes injected with PTZ-17 RNA. We also determined mouse chromosomal loci of the SEZ gene group and PTZ sensitive trait loci by linkage analysis for comparison with human synteny of epileptic families. The above-mentioned findings suggest that some herbal prescriptions will become promising drugs for the therapy against intractable nervous diseases which can not be ameliorated by pure chemical drugs in the future.
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PMID:[Cellular mechanism of seizure discharge and its normalization by a herbal mixture prescription "saikokeishito-ka-shakuyaku" (SK)]. 1136 Apr 85

The association of essential trace elements with epileptic seizures is poorly understood. On the basis of the evidences that the release of zinc from the brain of epilepsy (EL) mice, an animal model of genetically determined epilepsy, is enhanced by the induction of seizures and that alteration of zinc homeostasis is responsive to susceptibility to seizures, the distribution of trace elements in the brain was studied using EL mice and ddY mice, which form the genetic background for the inbred EL mice. The multitracer technique was applied to determine the distribution of trace elements. Twenty-four hours after intravenous injection of the multitracer, the concentration of 65Zn and 56Co in the brain of untreated EL mice was higher than in ddY mice, while the concentration of 65Zn and 56Co in the brain was decreased in seized EL mice. 75Se concentration in the hippocampus, cerebral cortex and cerebellum of untreated EL mice was lower than in ddY mice, while 75Se concentration in the hippocampus was increased in seized EL mice. 83Rb, an element of homologous series to potassium, concentration in the hippocampus and cerebral cortex of untreated EL mice was lower than in ddY mice, and 83Rb concentration in the cerebral cortex was decreased in seized EL mice. The movement of zinc, cobalt and selenium in the brain may be altered by enhancement of susceptibility to seizures. These results suggest that alteration of homeostasis of zinc, cobalt and selenium in the brain may be involved in the susceptibility, development or termination of seizures in EL mice.
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PMID:Distribution of trace elements in the brain of EL (epilepsy) mice. 1235 Mar 86


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