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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Light and electron microscopy (with the combined oxalate-pyroantimonate technique for the electron microscopic visualization of intracellular calcium) were used to compare the hippocampal pathology in rats killed immediately after 1.5-2 h of L-allylglycine-induced seizures with that in rats allowed 15-60 min of a seizure-free "recovery" period before perfusion fixation. Following 1.5 h of seizure activity, cellular pathology included astrocytic swelling and dark cell degeneration of pyramidal and polymorphic neurons. This was accompanied by a marked increase in the amount of calcium pyroantimonate deposits, particularly in swollen and disrupted mitochondria of CA1 and CA3 basal dendrites and in certain neuronal cell bodies in the CA1 and CA3 regions and the hilus. After a seizure-free period of between 30 and 60 min the hippocampi showed almost complete recovery except for a few remaining dark, shrunken cells. The majority of these were presumed to be interneurons. The ultrastructural changes were consistent with the observations by light microscopy. By 60 min, excess calcium deposits had disappeared except in the dark cells in which intracellular vacuoles retained deposits. We conclude that most of the pathological changes observed after 1.5 h of L-allylglycine induced status epilepticus, including the mitochondrial calcium "overload" are reversible. At 1 h after termination of status epilepticus apparently irreversible pathology (dark cell change, "ischaemic cell change") concerns predominantly the polymorphic neurons.
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PMID:Status epilepticus: the reversibility of calcium loading and acute neuronal pathological changes in the rat hippocampus. 646 62

Using electron microscopy and the combined oxalate-pyroantimonate technique, free calcium ions were located in the hippocampus of control rats and of those that had undergone status epilepticus induced by L-allylglycine or bicuculline. The validity of this technique was established by the use of the calcium chelating agent ethylene glycol bis(beta-aminoethyl ether), N,N'-tetra-acetic acid and by an X-ray microanalytical technique. In control material, calcium deposits were visible in synaptic vesicles and multivesicular bodies, in parts of the Golgi apparatus, mitochondria, lysosomes, and in glial and neuronal nuclei. Following 2 h of status epilepticus, cellular pathology included astrocytic swelling, and dark cell degeneration of pyramidal neurons. This was accompanied by a marked increase in the amount of calcium pyroantimonate deposits, particularly in swollen and disrupted mitochondria of CA1 and CA3 basal dendrites, and in selected neuronal cell bodies in the CA1 and CA3-4 regions. We propose that enhanced calcium entry into neurons and consequent overloading of the capacity of mitochondria for calcium sequestration is part of the cytotoxic mechanism leading to selective neuronal loss in the hippocampus in status epilepticus.
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PMID:Intracellular calcium accumulation in rat hippocampus during seizures induced by bicuculline or L-allylglycine. 663 67

Using electron microscopy and the combined oxalate--pyroantimonate technique, calcium was located in hippocampal neurons of rats that had undergone L-allylglycine-induced status epilepticus. In control material, calcium deposits were prominent in nearly every synaptic vesicle, and to a lesser degree in mitochondria and the Golgi apparatus of pyramidal neurons and dentate granule cells. After status epilepticus, mitochondrial calcium deposits increased, particularly in the swollen mitochondria of the pyramidal cell bodies and basal dendrites of CA3 and CA1 neurones. These studies support the theory that enhanced calcium entry leading to calcium overload of mitochondria may be an important cytotoxic mechanism producing selective neuronal loss.
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PMID:Intracellular sites of early calcium accumulation in the rat hippocampus during status epilepticus. 711 Jun 39

We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry. Adult male rats were either electrically stimulated in the ventral hippocampus for 90 min or injected with kainic acid or lithium/pilocarpine. Animals were observed for behavioral changes for up to 6 hr and were killed 24 hr or 4 weeks after the experimental treatments. At 24 hr, all animals that had exhibited a bout of acute status epilepticus showed a consistent pattern of neuronal loss in the EC in Nissl-stained sections. Neurodegeneration was most pronounced in layer III of the medial Ec at all dorsoventral levels. A few surviving neurons were frequently present in the lesioned area. An identical pattern of nerve cell loss was also seen in the EC of rats killed 4 weeks following the treatments. This lesion was completely prevented by an injection of diazepam and pentobarbital, given 1 hr after kainic acid administration. Immunohistochemistry demonstrated a relative resistance of parvalbumin-positive neurons in layer III of the medial EC. Taken together, these experiments indicate that prolonged seizures cause a preferential neuronal loss in layer III of the medial EC and that this lesion may be related to a pathological elevation of intracellular calcium ion concentrations.
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PMID:Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. 747 96

A 72-year-old woman was referred to hospital for obnubilation with general muscle weakness and hypotonia. Biology showed hypocalcemia, hypophosphatemia, increased serum creatine kinase and alkaline phosphatase levels. Brain CT scan, cerebrospinal fluid examination, and electromyogram were normal. Clinical status and electroencephalogram were consistent with non-convulsive generalized status epilepticus. The treatment included clonazepam and CaCl2 and consciousness returned to normal. A treatment with multivitamin infusion containing vitamin D2 was given for 3 weeks. Muscle weakness improved partially. Serum vitamin D3 level was low and osteomalacic myopathy was diagnosed. A treatment was given with 25OH vitamin D3, 50 micrograms per day. Two months later, serum vitamin D3 and creatine kinase levels were normal and the patient could walk without help. We conclude that vitamin D status should be monitored in elderly patients with muscle symptoms and abnormal calcium status. Osteomalacic myopathy should be considered in critically ill patients with muscle symptoms of an unclear cause.
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PMID:Muscle weakness in intensive care patients: initial manifestation of vitamin D deficiency. 770 75

Acetylcholine (ACh) is a powerful excitotoxic neurotransmitter in the brain. By stimulating Ca(2+)-mobilizing receptors, ACh, through G-protein(s), stimulates phospholipase C and causes the hydrolysis of a membrane phospholipid, phosphatidylinositol-4,5-bisphosphate to two second messengers, inositol-1,4,5-trisphosphate (ins-(1,4,5)-P3), and diacylglycerol. Ins-(1,4,5)-P3 is important in cholinergic neuronal stimulation, and injury. Cholinergic agonists cause tonic-clonic convulsions which may be either transient or persistent. Even short-term cholinergic convulsions may be associated with neuronal injury, especially in the basal forebrain and the hippocampus. Cholinergic-induced convulsions also elevate levels of brain Ca2+ which precede neuronal injury. Female sex and senescence increase the sensitivity of rats to cholinergic excitotoxicity. Even if cholinergic-induced brain phosphoinositide signalling is likely to trigger cholinergic excitotoxicity, several other processes may be involved in the ensuing neuronal injury. Once initiated, cholinergic convulsions cannot be stopped with cholinergic antagonists such as atropine even though they are effective when given prior to a cholinergic agonist. However, glutaminergic antagonists, and GABAergic agonists, are effective in the attenuation of ongoing cholinergic status epilepticus. Cholinergic brain stimulation may be, in fact, under a partial control of brain GABAergic tonus, but also cause the release of glutamate. Glutamate stimulates inositol lipid signalling in several neuronal cells and, therefore, underlines the significance of inositol lipid signalling in cholinergic-induced excitotoxicity. Moreover, the anatomical distribution of cholinergic brain damage correlates well with that of glutaminergic neurons. Furthermore, glutamate increases neuronal oxidative stress, i.e. it increases the levels of free intracellular calcium, the production of reactive oxygen species, and causes the depletion of neuronal glutathione. The role of excitatory amino acids as common mediators of cholinergic excitotoxicity may offer new insights into the neurotoxic consequences of cholinergic neuronal stimulation.
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PMID:Phosphoinositide second messengers in cholinergic excitotoxicity. 785 83

In adult rats, intraperitoneal administration of kainic acid, a glutamic acid analog and potent neurotoxin, induces persistent seizure activity that results in electrographic alterations and neuropathology that closely resemble human temporal lobe epilepsy. We used in situ hybridization to identify regions of altered glutamate and GABAA receptor gene expression following kainate-induced status epilepticus. In the CA3/CA4 area, the hippocampal region most vulnerable to neurodegeneration after kainate acid treatment, expression of GluR2 (the AMPA/kainate receptor subunit that limits Ca2+ permeability) and GluR3 was decreased markedly at 12 and 24 hr, times preceding neurodegeneration. These findings raise the possibility that increased formation of Ca(2+)-permeable AMPA/kainate receptors in the CA3/CA4 area may enhance glutamate pathogenicity. Expression of the GABAA alpha 1, subunit was also reduced, indicating a possible decrease in inhibitory transmission, which would also enhance excitotoxicity. GluR1 and NR1 expression was not significantly changed. In the dentate gyrus, a region resistant to neurodegeneration, concomitant increases in GluR2 and GluR3 expression were observed; GluR1, NR1, and GABAA alpha 1 mRNAs were not detectably altered. Analysis of emulsion-dipped sections revealed that the changes in GluR2, GluR3, and GABAA alpha 1 expression represented changes in mRNA content per neuron and were specific to pyramidal cells of the CA3/CA4 area and to granule cells of the dentate gyrus. These findings indicate that kainate seizures modify hippocampal glutamate and GABAA receptor expression in a cell-specific manner. Timing of the changes in glutamate and GABAA receptor mRNAs indicates that these changes may play a causal role in hippocampal neuronal cell loss following kainate-induced seizures.
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PMID:Kainate-induced status epilepticus alters glutamate and GABAA receptor gene expression in adult rat hippocampus: an in situ hybridization study. 818 36

Serum, cerebrospinal fluid (CSF) and urinary levels of magnesium and calcium and RBC magnesium levels were studied in 100 patients of idiopathic generalised tonic clonic seizures and 95 healthy controls matched for age and sex. There was a significant reduction in serum, CSF and RBC magnesium levels and a rise in serum and CSF calcium levels in epileptic patients. The 24 h urinary excretion of calcium and magnesium in the epileptics did not differ from controls. Post ictal (within 24 h of seizure) serum and CSF magnesium levels were significantly lower and calcium levels significantly higher as compared to inter ictal levels (4 wk after seizure). There was no correlation between serum magnesium, serum calcium and CSF calcium levels and the frequency, control or duration of fits. Low CSF magnesium levels correlated with increased frequency, poor control and longer duration of fits. Patients with status epilepticus and those in the EEG abnormalities had low CSF magnesium levels.
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PMID:Serum, CSF, RBC & urinary levels of magnesium & calcium in idiopathic generalised tonic clonic seizures. 822 53

Human status epilepticus (SE) is consistently associated with cognitive problems, and with widespread neuronal necrosis in hippocampus and other brain regions. In animal models, convulsive SE causes extensive neuronal necrosis. Nonconvulsive SE in adult animals also leads to widespread neuronal necrosis in vulnerable regions, although lesions develop more slowly than they would in the presence of convulsions or anoxia. In very young rats, nonconvulsive normoxic SE spares hippocampal pyramidal cells, but other types of neurons may not show the same resistance, and inhibition of brain growth, DNA and protein synthesis, and of myelin formation and of synaptogenesis may lead to altered brain development. Lesions induced by SE may be epileptogenic by leading to misdirected regeneration. In SE, glutamate, aspartate, and acetylcholine play major roles as excitatory neurotransmitters, and GABA is the dominant inhibitory neurotransmitter. GABA metabolism in substantia nigra (SN) plays a key role in seizure arrest. When seizures stop, a major increase in GABA synthesis is seen in SN postictally. GABA synthesis in SN may fail in SE. Extrasynaptic factors may also play an important role in seizure spread and in maintaining SE. Glial immaturity, increased electronic coupling, and SN immaturity facilitate SE development in the immature brain. Major increases in cerebral blood flow (CBF) protect the brain in early SE, but CBF falls in late SE as blood pressure falters. At the same time, large increases in cerebral metabolic rate for glucose and oxygen continue throughout SE. Adenosine triphosphate (ATP) depletion and lactate accumulation are associated with hypermetabolic neuronal necrosis. Excitotoxic mechanisms mediated by both N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors open ionic channels permeable to calcium and play a major role in neuronal injury from SE. Hypoxia, systemic lactic acidosis, CO2 narcosis, hyperkalemia, hypoglycemia, shock, cardiac arrhythmias, pulmonary edema, acute renal tubular necrosis, high output failure, aspiration pneumonia, hyperpyrexia, blood leukocytosis and CSF pleocytosis are common and potentially serious complications of SE. Our improved understanding of the pathophysiology of brain damage in SE should lead to further improvement in treatment and outcome.
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PMID:Pathophysiological mechanisms of brain damage from status epilepticus. 838 2

Calmodulin-kinase II (CaM kinase) is a calcium/calmodulin-dependent protein kinase which is highly enriched in the nervous system and mediates many of calcium's actions. Regulation of CaM kinase activity plays an important role in modulating synaptic transmission, synaptic plasticity and in neuropathology. Primary regulation of CaM kinase occurs via changes in intracellular calcium concentrations. Increased calcium stimulates protein kinase activity and induces autophosphorylation. Autophosphorylation of CaM kinase at specific sites results in altered activity and responsiveness to subsequent changes in calcium concentrations. Intracellular translocation of CaM kinase also appears to result from autophosphorylation. These mechanisms of regulation play an important role in synaptic plasticity (e.g., Aplysia ganglia), status epilepticus and cerebral ischemia. Long-lasting alterations in the expression of CaM kinase have been demonstrated in the kindling model of epilepsy and in monocular deprivation and therefore modulation of gene expression, in addition to autophosphorylation and translocation, appears to be another important mechanism of regulating CaM kinase activity.
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PMID:Regulation of type-II calmodulin kinase: functional implications. 838 27


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