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)

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

Current knowledge suggests integration of cerebral perfusion and metabolism as enabling normal neuronal function, and their pertubations explaining the brain damage of hypoxia, hypoglycaemia, hypoperfusion and status epilepticus. Similar mechanisms appear operative in the viral encephalopathies and cause psychomotor dysfunction and epilepsy. A transient inhibition of plasma membrane glucose transport is central to the understanding of the metabolic abnormalities of these encephalopathies, the ensuing cell energy crisis resulting from neuroglycopoenia being evidenced by electroencephalographic changes, lactic and ketoacidosis, hyperuricaemia and ionic aberrations. Failure of Na+ and Ca2+ pumps cause cerebral oedema and neuronal death respectively, the selective nature of the latter being due to alpha-adrenergic vasoconstriction. Management with hyperglycaemia-producing infusions and the judicious use of lactate and steroids can overcome the transport dysfunction and enable complete recovery. The temporal profile of the metabolic aberrations of febrile convulsions, which are the result of adaptation, provide a template supporting this mode of management of the severe encephalopathies.
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PMID:The probable mechanisms of brain damage and epilepsy in febrile convulsions, Singapore syndrome and Reye's syndrome. 250 20

Status epilepticus was induced in paralyzed, ventilated rats using bicuculline and was maintained for 50 to 120 minutes. Cerebral cortex, hippocampus, and cerebellum were assayed for calmodulin kinase II activity in vitro using [gamma-32P]ATP and polyacrylamide gel electrophoresis. Seizures resulted in a 3.2 fold decrease in calmodulin kinase activity in crude synaptic membranes of cortex and in a 8.2 fold decrease in hippocampal membranes. Cytosolic calmodulin kinase activity was slightly increased in rats in status epilepticus but statistical significance was not reached. Status epilepticus did not affect calcium/calmodulin-dependent kinase activity in cerebellar membranes or cytosol. These data suggest that intense firing associated with continuous seizure activity decreases calmodulin kinase activity in cortical and hippocampal synaptic membranes, which may result in altered neuronal excitability.
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PMID:Decreased calmodulin kinase activity after status epilepticus. 283 95

Light and electron microscopy were used to study the effect of hypoglycaemia on selectively vulnerable neurons of rat hippocampus with and without pharmacologic blockade of the N-methyl-D-aspartate (NMDA)-preferring receptor with 2-amino-7-phosphonoheptanoic acid (AP-7). In control hypoglycaemic hippocampi, dark cell change occurs predominantly in dentate granule cells. The topography and ultrastructural appearance of these changes is distinct from that produced by ischaemia or status epilepticus. In hypoglycaemia, mitochondrial calcium accumulation characteristic of ischaemia or status epilepticus is not seen. NMDA receptor blockade markedly attenuates the hypoglycaemic cell injury. Similar attenuation of ischaemic and epileptic brain damage by NMDA receptor blockade suggest that excessive neuronal excitation is a common mechanism of injury in each of the three conditions.
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PMID:Excitotoxic mechanisms in hypoglycaemic hippocampal injury. 303 25

The usefulness of the anticonvulsant drugs is determined by the mechanisms by which the agent acts and its pharmacokinetics. The general mechanisms of action of these agents include (1) effects on neurotransmitter action, (2) effects on repetitive neuronal firing mechanisms, (3) effects on neuronal networks, and (4) effects on neuronal ionic transport. Ethosuximide, valproic acid and clonazepam are used primarily in absence epilepsy. Valproic acid is also effective against generalized tonic-clonic epilepsy. Diazepam is used primarily in status epilepticus. Valproic acid enhances gamma aminobutyric acid (GABA)-mediated inhibition, reduces repetitive firing, and reduces both inhibition and excitation in neuronal networks. Clonazepam and diazepam enhance the inhibitory action of GABA, decrease inhibition in neuronal networks and affect calcium ion transport with lesser effects on repetitive firing. Ethosuximide reduces inhibition in neuronal networks, may interact with dopamine, and possibly affects sodium and potassium ion transport. Further work is needed to assess the degree of involvement of these effects in the anticonvulsant action versus the adverse effects of these agents.
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PMID:Mechanisms of anticonvulsant drug action. II. Drugs primarily used for absence epilepsy. 310 94

To understand better the molecular and cellular events associated with status epilepticus, a multifaceted analysis has begun on hippocampal tissues therapeutically removed from patients with temporal lobe epilepsy. In this first study, quantitative changes in major ganglioside species are reported, as well as the immunocytochemical localization on the ganglioside GD3 in epileptic human hippocampus. Although significant variations were found between patients, the pattern of change was consistent when compared to normal values obtained from an autopsied specimen and the literature. Total ganglioside content was reduced in epileptic hippocampi, which was attributable, in part, to pyramidal cell loss found in CA1 and CA3. In each case, the percentage of ganglioside GD3 was increased significantly, while ganglioside GD1a decreased. The former change is probably associated with reactive astrocytosis and the latter with loss of neuronal dendrites. Immunocytochemical localization revealed GD3 in the stratum radiatum and the subgranular layer of the dentate gyrus. In these areas, GD3 was present in punctate structures and astrocytes. These findings indicate that GD3 increases in selected areas of the sclerotic hippocampus and is presumably related to localized accumulation of reactive glial cells. Since gangliosides have a high affinity for calcium and localized increase in extracellular calcium could disrupt normal neuronal function, the localized increase in GD3 may not only denote reactive glial cells but may contribute directly to the altered, hyperexcitable condition of epilepsy.
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PMID:Ganglioside changes associated with temporal lobe epilepsy in the human hippocampus. 355 91

We previously demonstrated that the dihydropyridine calcium channel blocker, nimodipine, is an effective anticonvulsant in experimental seizures when administered parentally. Reported now are the results for the oral administration of nimodipine in pentylenetetrazole (PTZ)-induced seizures in the rabbit. Twenty rabbits were randomly assigned into 10 controls and 10 treated with nimodipine 5 mg/kg/day orally for 5 days. All animals received increasing doses of the convulsant PTZ intravenously (i.v). The epileptogenecity of this agent was assessed in all animals (mg/kg) by four electrocorticographic criteria: first seizure greater than 5 s, two seizures within 5 min, epileptiform activity for 1 h, and status epilepticus. In all four categories, nimodipine increased the seizure threshold by 50-60%. The dose of PTZ required to produce the first seizure was 27.0 +/- 5.4 mg/kg in controls and 49.6 +/- 9.9 mg/kg in treated animals (p less than 0.001). Similar values were obtained for the other three electrocorticographic categories. There were no observable adverse side effects. The results confirm our previous findings that calcium influx is critical for seizure induction, and that selective central nervous system (CNS) calcium channel blockers may emerge as a new class of anticonvulsants.
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PMID:Suppression of pentylenetetrazole seizures by oral administration of a dihydropyridine Ca2+ antagonist. 362 16

Because they induce similar neuropathological changes (ischaemic cell change with microvacuolization), it has been suggested that ischaemia, status epilepticus and hypoglycaemia produce cell death by similar mechanisms, especially those resulting from intracellular calcium accumulation. We have recently demonstrated microvacuolation of neurons, mitochondrial swelling (the electron microscopic correlate of microvacuolization) and massive mitochondrial calcium sequestration (using the pyroantimonate technique) following ischaemia or status epilepticus. We therefore studied the selectively vulnerable neurons of rat hippocampus by light and electron microscopy (including the pyroantimonate technique) following 30 and 60 min of EEG isoelectricity resulting from insulin hypoglycaemia. The neuropathology at the light and EM level is unique and different from that following status epilepticus or ischaemia. The most constant finding is dark cell change of the granule cells at the tip of the dentate gyrus. In contrast to status epilepticus and ischaemia, hippocampal pyramidal neurons are far less frequently involved. Microvacuoles are rarely seen and, when present, their ultrastructural correlate is swollen Golgi apparatus, not dilated mitochondria. No intracellular calcium accumulation is demonstrable with pyroantimonate technique. Thus the cellular alterations produced by hypoglycaemia differ in character and distribution from those produced by anoxia-ischaemia. Mitochondrial calcium accumulation is not prominent in cell death from hypoglycaemia. Whether calcium toxicity plays another, subtler role in hypoglycaemic brain injury is unknown.
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PMID:Neuronal alterations in hippocampus following severe hypoglycaemia: a light microscopic and ultrastructural study in the rat. 370 53

Status epilepticus may be followed by the loss of selectively vulnerable neurons in the hippocampus and neocortex. The acute cytopathology preceding cell loss is that of "ischemic cell change" or "dark cell change." In the hippocampus, selectively vulnerable neurons (CA3 and CA1 pyramidal neurons, hilar polymorphic neurons) show swelling of mitochondria in the perikaryon and dendrites after 30 to 120 min of seizure activity. Electron-microscopic studies with the combined oxalate/pyroantimonate technique reveal dense calcium pyroantimonate deposits in the swollen mitochondria. Suppression of seizure activity for 30 to 60 min is sufficient to allow recovery of normal mitochondrial morphology and calcium load. A small proportion of vulnerable neurons develop ischemic cell change with multiple vacuoles containing calcium pyroantimonate deposits. Neurons prone to burst firing accumulate calcium during seizures, and eventually show massive "overloading" of mitochondria. Although by analogy with studies in muscle a cytotoxic role for raised cytosolic calcium concentration has been proposed, the link between increased [CA2+] activation of phospholipases and proteinases and ischemic cell change remains uncertain.
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PMID:Cell damage in epilepsy and the role of calcium in cytotoxicity. 370 26

Injection of small volumes of calcium solution into the lateral ventricle of the cat wa followed by large electrical-impedance changes in gray matter bounding the ventricle, including the caudate nucleus and hippocampus. These changes lasted more than 24 hours and were accompanied by epileptiform electroencephalographic activity. Biweekly injections led to status epilepticus. Injections of similar amounts of magnesium ions were without comparable effects. Possible interactions between calcium ions and intercellular macromolecular material are discussed as a basis for certain impedance shifts in cerebral tissue.
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PMID:Periventricular cerebral impedance after intraventricular injection of calcium. 592 77


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