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)

Results from experiments performed with permanent non-neuronal cell lines suggest that endoplasmic reticulum (ER) calcium homeostasis plays a key role in the control of protein synthesis (PS). It has been concluded that disturbances in ER calcium homeostasis may contribute to the suppression of PS triggered by a severe metabolic stress (W. Paschen, Med. Hypoth., 47 (1996) 283-288). To elucidate how an emptying of ER calcium stores of these cells would effect PS and ribosomal aggregation of non-transformed fully differentiated cells, experiments were run on primary neuronal cell cultures. ER calcium stores were depleted by treating cells with thapsigargin (TG, a selective, irreversible inhibitor of ER Ca(2+)-ATPase), cyclopiazonic acid (CPA, a reversible inhibitor of ER Ca(2+)-ATPase), or caffeine (an agonist of ER ryanodine receptor). Changes in intracellular calcium activity were evaluated by fluorescence microscopy using fura-2-loaded cells. Protein synthesis was determined by measuring the incorporation of [3H]leucine into proteins. The degree of aggregation of ribosomes was evaluated by electron microscopy. TG induced a permanent inhibition of PS to about 10% of control which was only partially reversed within 2 h of recovery. CPA caused about 70% inhibition of PS, and PS recovered completely 60 min after treatment. Caffeine produced an inhibition of PS to about 50% of control. Loading cells with the calcium chelator BAPTA-AM (33.3 microM) alone suppressed PS without reversing TG- or caffeine-induced inhibition of PS, indicating that the suppression of PS was caused by a depletion of ER calcium stores and not by an increase in cytosolic calcium activity. TG-treatment of cells induced a complete disaggregation of polysomes which was not reversed within the 4 h recovery period following TG-treatment. After caffeine treatment of cells, we observed a heterogenous pattern of ribosomal aggregation: in some neurons ribosomes were almost completely aggregated while in other cells a significant portion of polyribosomes were disaggregated. The results indicate that a depletion of neuronal ER calcium stores disturbs protein synthesis in a similar way to the effects of transient forms of metabolic stress (ischemia, hypoglycemia or status epilepticus), thus implying that a disturbance in ER calcium homeostasis may contribute to the pathological process of stress-induced cell injury.
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PMID:Relation of neuronal endoplasmic reticulum calcium homeostasis to ribosomal aggregation and protein synthesis: implications for stress-induced suppression of protein synthesis. 943 27

Postictal cognitive impairment following seizures can last from minutes to days and be disabling to the patient. The purpose of this study was to compare the behavioral features of seizures with postictal memory impairment in young seizure-naive rats and rats with a prior history of status epilepticus (SE) and examine the relationship between postictal EEG changes and cognitive recovery. Following training in the water maze to asymptote levels of learning, rats with a prior history of SE and seizure-naive rats had flurothyl-induced generalized seizures and time to recovery to baseline was then measured. Following generalized seizures rats had impaired performance in the water maze with the duration of the cognitive deficits exceeding the length of the seizure. There was not a close relationship between duration of cognitive impairment and either latency to onset of seizure or duration. The animal's neurological status was a factor in the duration of cognitive impairment following seizures; while there were no differences between SE and seizure-naive rats in latency to seizure onset or duration of the seizures, animals with a prior history of SE had a longer period of impairment following a seizure than animals without such a history. Postictal cognitive impairment was associated with changes in theta activity in animals with a prior history of SEs but not in seizure-naive animals. Caffeine, when administered following the seizure, reduced postictal cognitive impairment in a dose-dependent manner. This study demonstrates that duration of postictal cognitive impairment is not directly related to duration of the seizure. The neurological status of the animal is a determining factor in duration of postictal impairment.
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PMID:Effect of the postictal state on visual-spatial memory in immature rats. 1297 71

To try to identify the critical structures during epileptogenesis, we used the lithium-pilocarpine model that reproduces most clinical and neuropathological features of temporal lobe epilepsy (TLE). We used imaging techniques as well as a disease modifying approach and pharmacological strategy. With [14C]-2-deoxyglucose autoradiography, we assessed changes in cerebral glucose utilization. T2-weighted magnetic resonance imaging (MRI, 4.7 T) allowed follow-up of structures involved in epileptogenesis. A potential disease-modifying effect was studied using preconditioning with brief seizures (amygdala kindling, maximal electroshocks) and pharmacological strategies including vigabatrin (250 mg/kg), caffeine (0.3 g/L in drinking water), topiramate (10-60 mg/kg), pregabalin (50 mg/kg followed by 10 mg/kg), or RWJ-333369 (10-120 mg/kg). In adult and PN21 rats that became epileptic, entorhinal, and piriform cortices were the initial structures exhibiting significant signal changes on MRI scans, from 6 h after status epilepticus (SE) onset, reflecting neuronal death. In PN21 rats that did not become epileptic, no signal occurred in parahippocampal cortices. In hippocampus, MRI signal change appeared 36-48 h after SE, and progressively worsened to sclerosis. During the latent and chronic phases, the metabolic level in the hilus of adult and PN21 epileptic rats was normal although neuronal loss reached 60-75%. Protection limited to CA1 and/or CA3 (caffeine, topiramate, vigabatrin, amygdala kindling) did not affect the latency to spontaneous seizures. Protection limited to the entorhinal and piriform cortices (pregabalin) delayed epileptogenesis. The combined protection of Ammon's horn and parahippocampal cortices (RWJ-333369) prolonged the latency before the onset of seizures in a dose-dependent manner or, in some cases, prevented the epilepsy. The entorhinal and piriform cortices are critically involved in the early phase of the epileptogenesis while the hilus may initiate and/or maintain epileptic seizures. Pharmacological protection of the basal cortices is necessary for a beneficial disease-modifying effect but this must be combined with protection of the hippocampus to prevent epileptogenesis in this model of TLE.
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PMID:Pathogenesis and pharmacology of epilepsy in the lithium-pilocarpine model. 1791 May 80