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)

In order to assess acute, short and long-term effects of seizures in the immature rat brain, we studied the metabolic, circulatory and histopathological changes induced by pentylenetetrazol (PTZ) given at postnatal day 10 (P10) or 21 (P21). Seizures were induced by repetitive subconvulsive injections of PTZ given as a first dose of 40 mg/kg followed 10 min later by 20 mg/kg. Thereafter, rats received every 10 min additional injections of PTZ 10 mg/kg until the onset of status epilepticus. Local cerebral metabolic rates for glucose (LCMRglc) were measured both during the seizures in P10 and P21 rats and in the young adult animal at P60 by means of the quantitative 2-deoxyglucose technique. Rates of local cerebral blood flow (LCBF) were determined during the seizures by the iodoantipyrine technique. Short-term histological changes were assessed by acid fuchsin and hematoxylin-eosin staining and by HSP72 immunohistochemistry. At P10, LCMRglcs uniformly increased (38-400%) over control values during seizures. At P21, metabolic increases (39-181%) occurred only in 20% of the structures while LCMRglcs decreased in most cortical, hippocampal and sensory areas as well as in mammillary body, discrete thalamic nuclei and white matter areas. At P10, LCBF rose (32-184%) in all brain structures whereas, at P21, LCBF decreased in cortical, hippocampal and sensory regions and increased in most other areas. At P60, in animals having seized at either age, significant long-term decreases in LCMRglcs were recorded in hippocampus, auditory and piriform cortex, medial geniculate body and mammillary body. In P60 animals exposed to PTZ at P10, LCMRglcs were also decreased in 3 other sensory areas. In P60 animals exposed to seizures at P21, LCMRglcs were additionally decreased in sensory regions, cortices, thalamic and hypothalamic regions. Neuronal cells were transiently stained with acid fuchsin, with a peak occurring at 24 h after the seizures. The stain was visible in all regions of cerebral cortex and hippocampus and in some thalamic and hypothalamic nuclei. This transient staining was not accompanied by cell degeneration as assessed by hematoxylin-eosin histology. No HSP72 expression could be detected 24 h after the seizures, neither at P10 nor at P21. The present study shows that the immature rat neurons undergo altered metabolic rates and local circulatory decreases in the acute phase, a change in the affinity of acid fuchsin as a short-term effect and long-term metabolic decreases. All these changes are located in the same regions, i.e., cerebral cortex, hippocampus, sensory regions as well as scattered thalamic and hypothalamic nuclei. Thus, short- and long-term metabolic changes induced by seizures can be used as an index of cell stress in the immature rat brain. Since all these changes occur in the absence of visible neuronal death, they might be related to changes in the final arborization and synaptic organization of the developing brain.
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PMID:The model of pentylenetetrazol-induced status epilepticus in the immature rat: short- and long-term effects. 898 91

The study explored for the first time the quantitative dentate hilar cell damage in relation to the duration of limbic status epilepticus (SE) induced with electric stimulation on naive rats. SE was induced in adult S-D rats with electric stimulation delivered through a stimulating/recording electrode targeted at the right amygdala. Once SE was established, no further stimulation was given. The rats were treated with diazepam at various times to stop SE, and perfused 18 hours later. Naive and sham operated rats served as controls. Horizontal paraffin sections at the level of the ventral hippocampus were stained with acid fuchsin/cresyl violet. Irreversibly damaged neurons in the right dentate hilus were counted. Neuronal damage was absent with sham operation (n = 4, p > 0.05) and 30-min SE (n = 4, p > 0.05), but it became significant with 1 hour (n = 6, p < 0.05) and longer durations (n = 14, p < 0.05) of SE, compared with the naive controls (n = 10). The severity of SE-induced neuronal damage was not related to the current intensity, induction time, stimulation intensity, or number of class 3-5 seizures. We demonstrate for the first time the relation between seizure duration and the severity of dentate hilar cell damage in limbic SE induced by electric stimulation of naive rats. Further study of this model may elucidate the pathophysiology of SE and improve patient care.
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PMID:Dentate hilar cell damage in electric stimulation-induced limbic status epilepticus. 942 65

Status epilepticus (SE), an special epileptic syndrome, is a frequent neurological emergency (50/100,000) and a critical condition (mean mortality 22%, in 3% of pediatric patients and 38% in the elderly). Accepting its widest concept, it appears without history of epilepsy in 58%. Neuronal damage, mainly hypocampal, has been experimentally demonstrated in convulsive and nonconvulsive SE. We attempt to demonstrate that the most important prognostic factors are: age, more related to morbidity in children and in mortality in the elderly; etiology, determining the evolution in most cases, but not always: in the same etiological group, the coincidence of SE can increase threefold the mortality; the seizure type, especially the convulsive SE; patients with previous epilepsy have a better outcome; the epileptic syndrome, rather determinant of incidence and outcome of the SE in the childhood; the length of SE, but in the cases of outcome directly depending on the etiology; the evolutive phase in which treatment is started; the complications, mainly respiratory; the global therapeutical strategy and the adequate use of drugs, related to order, dosage and timing, are determinant of morbidity and mortality.
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PMID:[Prognosis in status epilepticus]. 947 Apr 40

Kainic acid (KA)-induced status epilepticus (SE) in adult rats results in extensive neuronal damage throughout the limbic system and the loss of selectively vulnerable neuronal populations, particularly CA3 neurons. We investigated the effects of a short episode of seizure activity on neuronal death elicited by a subsequent prolonged SE episode. A short episode of seizure activity was produced by sub-cutaneous (s.c.) injection of KA followed after 1 h by pentobarbital administration. Twenty-four hours later, KA was administered again, and animals were sacrificed 3 days later. Neuronal damage was estimated by visual analysis of neuronal density. Our results show that a short episode of seizure activity did not produce neuronal damage but almost completely protected vulnerable neurons from KA-induced neuronal damage. These results extend to epileptic tolerance the notion of tolerance previously described in the case of ischemia.
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PMID:A short episode of seizure activity protects from status epilepticus-induced neuronal damage in rat brain. 981 46

Prolonged and continuous epileptic seizures [status epilepticus (SE)] produce a widespread pattern of neuronal death, primarily in limbic brain regions. Because it has been suggested that seizure-induced neuronal death may be apoptotic in nature, we tested the hypothesis that lithium-pilocarpine-induced status epilepticus (LPCSE) produces apoptotic neurons. LPCSE lasting 3 h was induced in male Wistar rats which were allowed to recover for 24 or 72 h before perfusion-fixation. Neuronal death was assessed by light microscopy with the haematoxylin-and-eosin stain (H&E), with in situ DNA nick-end labelling (TUNEL stain), by electron microscopy, and by agarose gel electrophoresis of DNA extracted from vulnerable brain regions. Ultrastructurally, acidophilic neurons identified with H&E were dark, shrunken and necrotic in appearance, exhibiting pyknotic nuclei, irregular, dispersed chromatin clumps and cytoplasmic vacuolization. No cells with apoptotic features were seen. Acidophilic neurons were found in 21 out of 23 brain regions examined, and comprised 26-45% of the total number of neurons examined. A subset of these neurons (< 10% of the total number of neurons) were TUNEL-positive at 72 h, but not 24 h, after SE. Internucleosomal DNA cleavage (DNA 'laddering') was found in the six brain regions examined ultrastructurally 24 and 72 h after SE. These results indicate that, in adult rats, LPCSE produces neuronal injury with the appearance of necrosis rather than apoptosis. The necrotic neurons show nuclear pyknosis, chromatin condensation and internucleosomal DNA fragmentation, confirming the nonspecificity of these nuclear changes. Internucleosomal DNA cleavage and other programmed cell death mechanisms can be activated by SE in neurons which become necrotic.
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PMID:Lithium-pilocarpine-induced status epilepticus produces necrotic neurons with internucleosomal DNA fragmentation in adult rats. 1021 13

Neuronal damage in relation to the duration of seizure was studied in limbic status epilepticus (SE) induced by electric stimulation of naive rats. Adult Sprague-Dawley rats were stimulated at the right amygdala to induce SE. To stop the seizures, diazepam was given to different groups of rats at 0.5 h (n = 4), 1 h (n = 6), 2 h (n = 6), and 3-4 h (n = 8) of SE. Eighteen hours after the end of SE, the rats were perfusion fixed. Naive (n = 6) and sham-operated (n = 4) rats served as controls. Horizontal paraffin sections were stained with acid fuchsin and cresyl violet. Neuronal damage was absent after 30 min of SE. Status epilepticus of 1 h or longer duration regularly caused neuronal damage to the cerebral cortex, thalamus, hippocampus, amygdala, and pars reticulata of the substantia nigra. Damage in the cerebral cortex predominated in the entorhinal, temporal, and pyriform regions. In the hippocampus, the dentate hilus was most severely affected, followed by CA3 and CA1. Damage to the dentate granule layer was mild. Further studies of the pathophysiology of excitotoxicity may help to protect patients from sequels of status epilepticus such as neuronal damage and epilepsy.
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PMID:Neuropathology of limbic status epilepticus induced by electrical stimulation of naive rats. 1040 13

Systemic administration of pilocarpine and kainic acid (KA) has been extensively used to model temporal lobe epilepsy in rats. Here the regional distribution of selectively vulnerable neurons and the temporal evolution of such neuronal injury after status epilepticus (SE) are compared in both models. Using the silver staining technique of Gallyas, argyrophilic neurons were measured on a 0-3 (least-most) scale in 53 different brain areas. Few neurons were silver-stained 2.5 h after kainate-induced SE, but many silver-stained cells could be seen in most neocortical, hippocampal, amygdaloid and hypothalamic structures for pilocarpine group. In general, 8 or 24 h intervals between SE onset and perfusion times yielded the most intense neuronal silver-impregnation. Pilocarpine-induced neuronal silver impregnation was more prominent than that induced by kainate treatment for many areas in cortex, hippocampus, endopiriform nucleus, amygdaloid complex and hypothalamus. On the other hand, in the thalamus, some cortical areas, claustrum, lateral septum and caudoputamen, kainate-induced neuronal silver staining was also prominent, but occurred later than in pilocarpine-treated animals. Neuronal injury was found in almost the same brain areas in both models of SE but with different intensity levels and time course profiles. It was suggested that such differences in the temporal profile of cell damage should be taken into account when searching for neuroprotective agents.
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PMID:Temporal profile of neuronal injury following pilocarpine or kainic acid-induced status epilepticus. 1075 2

Prolonged seizures (status epilepticus) induced by kainic acid activate programmed cell death mechanisms, and it is believed that kainic acid-induced status epilepticus induces neuronal apoptosis. In order to test this hypothesis, adult rats were subjected to 3-h kainic acid-induced seizures, with 24- or 72-h recovery periods. Neuronal death was assessed by light microscopy with the Hematoxylin and Eosin stain and with in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL stain), by electron microscopy, and by agarose gel electrophoresis of DNA extracted from five vulnerable brain regions. Spontaneous and MK-801-induced apoptotic neurons from retrosplenial cortex of neonatal rats, evaluated by light and electron microscopy, were used as positive controls for apoptosis. Surprisingly, the large chromatin clumps of apoptotic neurons were TUNEL negative, whereas the cytoplasm showed light-to-moderate TUNEL staining, consistent with a lack of identifiable nuclear membranes ultrastructurally, and with intermingling of nuclear and cytoplasmic contents. Ultrastructurally, the acidophilic neurons produced by kainic acid-induced status epilepticus, identified with Hematoxylin and Eosin stain, were dark, shrunken and necrotic, with pyknotic nuclei containing small, dispersed chromatin clumps, and with cytoplasmic vacuoles, some of which were swollen, disrupted mitochondria. No apoptotic cells were seen. Acidophilic neurons were found in up to 20 of 23 brain regions examined and comprised 10-25% of the total number of neurons examined. A subset of these neurons (<10% of the total number of neurons in five of 23 regions) had TUNEL-positive nuclei 72h but not 24h after status epilepticus. Internucleosomal DNA cleavage (DNA "laddering") occurred in the four most damaged brain regions examined by electron microscopy 24h after SE and the three most damaged regions 72h after status epilepticus. Our results demonstrate that kainic acid-induced status epilepticus produces neuronal necrosis and not apoptosis in adult rats. The necrotic neurons show nuclear pyknosis, chromatin condensation and DNA laddering. Programmed cell death mechanisms activated by kainic acid-induced status epilepticus occur in neurons which become necrotic and could contribute to necrotic, as well as apoptotic, neuronal death.
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PMID:Kainic acid-induced seizures produce necrotic, not apoptotic, neurons with internucleosomal DNA cleavage: implications for programmed cell death mechanisms. 1085 10

Neuronal damage has been observed in the medial temporal lobe of both humans and animals following status epilepticus. The aim of the present study was to investigate the occurrence of medial temporal lobe damage in status epilepticus patients treated in hospital with a predetermined protocol and to assess whether the changes progress in a long-term follow-up. The volumes of the hippocampus, amygdala, entorhinal and perirhinal cortices were measured using magnetic resonance imaging (MRI) in nine adult patients with status epilepticus 3 weeks, 6 and 12 months after the insult. The control group included 20 healthy subjects. The etiology of status epilepticus was an acute process in one patient and a chronic process in eight cases. The mean duration of secondarily generalized tonic-clonic status epilepticus episodes was 1 h and 44 min. Volumetric MRI indicated that none of the patients developed marked volume reduction in the hippocampus, amygdala, or the entorhinal and perirhinal cortices during the 1-year follow-up period. Status epilepticus does not invariably lead to a progressive volume reduction in the medial temporal lobe structures of adult patients treated promptly in hospital with a predetermined protocol for rapid cessation of seizure activity.
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PMID:MRI volumetry of the hippocampus, amygdala, entorhinal cortex, and perirhinal cortex after status epilepticus. 1086 43

Status epilepticus is common and associated with significant mortality and complications. It affects approximately 50 patients per 100,000 population annually and recurs in >13%. History of epilepsy is the strongest single risk factor for generalized convulsive status epilepticus. More than 15% of patients with epilepsy have at least one episode of status epilepticus and low antiepileptic drug levels are a potentially modifiable risk factor. Other risks include young age, genetic predisposition, and acquired brain insults. Fever is a very common risk in children, as is stroke in adults. Mortality rates are 15% to 20% in adults and 3% to 15% in children. Acute complications result from hyperthermia, pulmonary edema, cardiac arrhythmias, and cardiovascular collapse. Long-term complications include epilepsy (20% to 40%), encephalopathy (6% to 15%), and focal neurologic deficits (9% to 11%). Neuronal injury leading to temporal lobe epilepsy is probably mediated by excess excitation via activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors and consequent elevated intracellular calcium that causes acute necrosis and delayed apoptotic cell death. Some forms of nonconvulsive status epilepticus may also lead to neuronal injury by this mechanism, but others may not. Based on clinical and experimental observations, complex partial status epilepticus is more likely to result in neuronal injury similar to generalized convulsive status epilepticus. Absence status epilepticus is much less likely to result in neuronal injury, and complications because it may be mediated primarily through excess inhibition. Future research strategies to prevent complications of status epilepticus include the study of new drugs (including NMDA antagonists, new drug delivery systems, and drug combinations) to stop seizure activity and prevent acute and delayed neuronal injury that leads to the development of epilepsy.
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PMID:Status epilepticus: risk factors and complications. 1088 37


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