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)

We studied patients with partial and primary generalized seizures using fluorine-18-labeled 2-fluorodeoxyglucose and positron emission tomography. Interictal studies of patients with partial seizures showed regions of focal or lateralized hypometabolism in 15 of 17 patients with unilateral electroencephalographic foci. Several patients had more than one hypometabolic region. In 1 patient PET hypometabolism was contralateral to the electroencephalographic epileptic focus. Six of 10 patients without definite electroencephalographic foci also showed unilateral PET hypometabolic regions. PET during complex partial seizures in 3 patients showed hypermetabolism at the site of the hypometabolic focus. A postictal scan in 1 patient showed extension of interictal temporal hypometabolism to the frontal lobe as well. Interictal scans in 8 patients with primary generalized seizures did not reveal any hypometabolic regions. One patient scanned during an attack of absence status epilepticus showed a slight decrease in metabolic rate compared to the interictal scan. Temporal lobectomy has been performed in 6 patients with focal PET hypometabolism. PET may obviate the need for depth electrode study in some patients with intractable partial seizures.
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PMID:The role of positron emission tomography in the evaluation of seizure disorders. 661 Nov 20

To investigate the progression of cellular injury in a model of hippocampal epileptogenesis, we used two histochemical methods reported to specifically label injured neurons, the Dark Neuron stain and Fluoro-Jade. Pilocarpine was administered systemically (380mg/kg i.p.) to induce status epilepticus. The duration of status epilepticus was controlled to last 1h by stopping it with diazepam (4mg/kg i.p.). The progression of cellular damage was quantified at six specific time points following the initial pilocarpine-induced insult: 3h, 6h, 12h, 24h, one week, and three weeks. To assess, in parallel, neuronal loss in specific hippocampal regions throughout epileptogenesis, the neuronal nuclear protein NeuN was used as a specific marker of neurons. Results revealed a different time-dependent progression of Dark Neuron and Fluoro-Jade labelling following status epilepticus. A significantly greater proportion of silver-impregnated cells labelled by the Dark Neuron stain was quantified in the stratum radiatum and stratum pyramidale of CA1 at the early time point of 3h compared with the proportion of Fluoro-Jade labelling in adjacent sections. In contrast, the maximal staining with Fluoro-Jade appeared at a later stage during epileptogenesis (between 24h and one week), with a significantly greater proportion of neurons labelled compared to the Dark Neuron stain in the stratum radiatum of CA1, stratum pyramidale of CA1, stratum radiatum of CA3 and the polymorphic layer of the dentate gyrus. Neurons from control animals were not significantly labelled by either of the two staining methods. Interestingly, the increase in Fluoro-Jade labelling corresponded in time to neuron loss. The two stains therefore appear to highlight separate processes of neuronal damage. This finding indicates that distinct cellular events take place at different stages of epileptogenesis, which may differ considerably from the permanent changes observed in chronically epileptic tissue.
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PMID:Differential progression of Dark Neuron and Fluoro-Jade labelling in the rat hippocampus following pilocarpine-induced status epilepticus. 1077 39

The excitatory amino acid glutamate has been implicated in the neurodegeneration associated with several different central nervous system diseases. Treatment with kainic acid (KA), a glutamate analog known to activate the AMPA/KA subtype of glutamate receptor, has been widely used as a model of epilepsy. Long term temporal studies of its neuropathological effects, however, are lacking. In this study, two techniques were used to directly visualize and characterize the neuropathology that occurred over a 2-month period following KA-induced status epilepticus in adult female Sprague-Dawley rats. Post-injection survival was 2, 4, 8 h, 2 days, 2 weeks, or 2 months. Labeling with Fluoro-Jade B (FJB), a fluorescent green dye that labels the cell body, dendrites, axons and axon terminals of degenerating neurons, was observed within the cortex, hippocampus, thalamus, basal ganglia, and amygdala by 4 h post-treatment. The highest level of labeling was seen in the piriform cortex, hippocampus, and thalamus. Myelin changes in the rat forebrain following KA treatment were also examined using the myelin-specific Black-Gold (BG) stain. Varicose myelinated fibers were observed in the same regions as FJB positive neurons, although these changes were evident by the 2-h survival time-point. Both stains showed a temporal progression of brain damage throughout the affected areas. By 2 months post-treatment, few degenerating neurons could be detected and abnormal myelin was absent in most regions. As myelin changes can be seen prior to neuronal degeneration, and oligodendrocytes express functional AMPA/kainate-type glutamate receptors, the neurodegeneration and myelin pathologies may occur as independent events. Thus, researchers should consider the temporal and multiple effects of kainic acid to optimize conditions for their endpoint of interest when designing experiments.
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PMID:Temporal progression of kainic acid induced neuronal and myelin degeneration in the rat forebrain. 1079 88

Status epilepticus (StE) in immature rats causes long-term functional impairment. Whether this is associated with structural alterations remains controversial. The present study was designed to test the hypothesis that StE at an early age results in neuronal loss. StE was induced with lithium-pilocarpine in 12-d-old rats, and the presence of neuronal damage was investigated in the brain from 12 hr up to 1 week later using silver and Fluoro-Jade B staining techniques. Analysis of the sections indicated consistent neuronal damage in the central and lateral segments of the mediodorsal nucleus of the thalamus, which was confirmed using adjacent cresyl violet-stained preparations. The mechanism of thalamic damage (necrosis vs apoptosis) was investigated further using TUNEL, immunohistochemistry for caspase-3 and cytochrome c, and electron microscopy. Activated microglia were detected using OX-42 immunohistochemistry. The presence of silver and Fluoro-Jade B-positive degenerating neurons in the mediodorsal thalamic nucleus was associated with the appearance of OX-42-immunopositive activated microglia but not with the expression of markers of programmed cell death, caspase-3, or cytochrome c. Electron microscopy revealed necrosis of the ultrastructure of damaged neurons, providing further evidence that the mechanism of StE-induced damage in the mediodorsal thalamic nucleus at postnatal day 12 is necrosis rather than apoptosis. Finally, these data together with previously described functions of the medial and lateral segments of the mediodorsal thalamic nucleus suggest that some functions, such as adaptation to novelty, might become compromised after StE early in development.
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PMID:Status epilepticus causes necrotic damage in the mediodorsal nucleus of the thalamus in immature rats. 1133 88

The present study was designed to address the question of whether recurrent spontaneous seizures cause progressive neuronal damage in the brain. Epileptogenesis was triggered by status epilepticus (SE) induced by electrically stimulating the amygdala in rat. Spontaneous seizures were continuously monitored by video-EEG for up to 6 months. The progression of damage in individual rats was assessed with serial magnetic resonance imaging (MRI) by quantifying the markers of neuronal damage (T2, T1 rho, and Dav) in the amygdala and hippocampus. The data indicate that SE induces structural alterations in the amygdala and the septal hippocampus that progressively increased for approximately 3 weeks after SE. T2, T1 rho, and Dav did not normalize during the 50 days of follow-up after SE, suggesting ongoing neuronal death due to spontaneous seizures. Consistent with these observations, Fluoro-Jade B-stained preparations revealed damaged neurons in the hippocampus of spontaneously seizing animals that were sacrificed up to 62 days after SE. The presence of Fluoro-Jade B-positive neurons did not, however, correlate with the number of spontaneous seizures, but rather with the time interval from SE to perfusion. Further, there were no Fluoro-Jade B-positive neurons in frequently seizing rats that were perfused for histology 6 months after SE. Also, the number of lifetime seizures did not correlate with the severity of neuronal loss in the hilus of the dentate gyrus assessed by stereologic cell counting. The methodology used in the present experiments did not demonstrate a clear association between the number or occurrence of spontaneous seizures and the severity of hilar cell death. The ongoing hippocampal damage in these epileptic animals detected even 2 month after SE was associated with epileptogenic insult, that is, SE rather than spontaneous seizures.
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PMID:Progression of neuronal damage after status epilepticus and during spontaneous seizures in a rat model of temporal lobe epilepsy. 1214 71

Various studies demonstrated that the neurotransmitter norepinephrine (NE) plays a relevant role in modulating seizures; in particular, a powerful effect consists in delaying the kindling of limbic areas such as the amygdala and hippocampus. Given the rich NE innervation of limbic regions, we selected a sensitive trigger area, the anterior piriform cortex, to test whether previous loss of noradrenergic terminals modifies sporadic seizures in rats. The damage to locus coeruleus terminals was produced by using the selective neurotoxin N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 60 mg/kg i.p.). In intact rats, bicuculline (a GABA-A antagonist, 118 pmol) microinfused into this area produced sporadic seizures, while in rats previously injected with DSP-4, bicuculline determined long-lasting self-sustaining status epilepticus. In intact rats, sporadic seizures were accompanied by a marked increase in norepinephrine release in the contralateral piriform cortex, while in locus coeruleus-lesioned rats this phenomenon was attenuated. While bicuculline-induced sporadic seizures were prevented by the focal infusion of amino-7-phosphonoheptanoic acid (AP-7, a selective NMDA antagonist), or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulphonamide (NBQX, a selective non-NMDA antagonist), status epilepticus obtained in norepinephrine-lesioned rats was insensitive to AP-7 but was still inhibited by NBQX. By using fluorescent staining for damaged (Fluoro-Jade B) and intact (DAPI) neurons, as well as cresyl violet, we found that rats undergoing status epilepticus developed neuronal loss in various limbic regions. This study demonstrates a powerful effect of noradrenergic terminals in regulating the onset of limbic status epilepticus and its sensitivity to specific glutamate antagonists.
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PMID:A damage to locus coeruleus neurons converts sporadic seizures into self-sustaining limbic status epilepticus. 1282 66

Absence seizures are traditionally believed to have no significant long-term neurological consequences, but few basic scientific studies have examined the effects of absence seizures on neuronal function, especially regarding absence status epilepticus. We developed a model of generalized nonconvulsive status epilepticus (GNCSE) in rats to study behavioral, functional, and histological effects of GNCSE. Using repetitive timed injections of low-dose pentylenetetrazol (PTZ), a state of prolonged behavioral arrest and immobility associated with frequent generalized spike-wave discharges on EEG could be induced for hours, consistent with GNCSE. GNCSE occurred reproducibly in adult rats, but surprisingly not in juvenile rats or adult mice. There was no evidence of pathological damage following GNCSE using Fluoro-Jade B and Cresyl Violet histological methods. Although a transient, subtle deficit in place learning occurred in PTZ-treated rats, there were no long-term behavioral effects of GNCSE on spatial learning or sensorimotor function. However, 1 week after a single episode of GNCSE, there was an increase in absence seizures in response to a repeat dose of PTZ compared to controls. These results indicate that an animal model of GNCSE can be generated and that even in the absence of overt neuronal damage, GNCSE may produce functional changes in neurons that alter electrical excitability of neural circuits.
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PMID:An animal model of generalized nonconvulsive status epilepticus: immediate characteristics and long-term effects. 1295 92

It is in dispute whether caspase 3 contributes to status epilepticus (SE)-induced cell loss. We hypothesized that caspase 3-mediated cell death continues beyond the acute phase of SE. We induced SE with either kainic acid or electrical stimulation of the amygdala in Wistar and Sprague-Dawley rats. Caspase 3 immunohistochemistry, Western blot analysis and enzyme activity measurements were used to determine cellular localization and the time course of caspase 3 expression and activation. Immunohistochemistry indicated that caspase 3 protein expression increased following SE, peaking at 16-24 h. Cleavage of procaspase 3 to active fragments (p20-17) was detected 2-7 days after SE. Caspase 3 enzyme activity was elevated at 8 h and further increased up to 19.4-fold at 7 days following SE. Activation of caspase 3 after SE occurred in the hippocampus and the extrahippocampal temporal lobe but not in the thalamus. Caspase 3-immunoreactive cells represented only a minority of degenerating cells as assessed by Fluoro-Jade B and TUNEL staining. Analysis of double-labelled sections indicated that active caspase 3 was located in astrocytes rather than neurons or microglia. There was increased caspase 3 expression in both rat strains, and it was independent of the method used to induce SE. These data demonstrate that caspase 3 contributes to the cell death occurring within the first week after SE, but in only a small proportion of degenerating cells. These results suggest that, contrary to expectations, caspase 3 inhibitors would have only limited benefits in the treatment of SE.
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PMID:Expression and activation of caspase 3 following status epilepticus in the rat. 1451 28

Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging-related differences in the effect of prolonged SE on the expression of hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was performed on hippocampal sections using antibodies directed against the alpha1 subunit of class A-D VGCCs. Compared to age-matched controls, SE animals showed a marked loss of alpha1A immunoreactivity (IR) in CA3 and the hilus, which was more prominent in aged animals. Alpha1B-IR was decreased selectively in the stratum lucidum of CA3. Alpha1C-IR was increased on neuronal somata in the pyramidal and granule cell layers of both age groups. In contrast, there was a marked decrease of alpha1C-IR in the neuropil of CA3 stratum pyramidale and portions of CA1, which was more pronounced in aged animals. Alpha1D-IR was decreased in CA3 and the hilus, which was more prominent in aged animals. Nissl staining demonstrated mild somal dysmorphia in the pyramidal cell layer of CA3, which was more apparent in aged animals. Fluoro-Jade B staining was prominent in the stratum pyramidale of CA3 and in the hilus of aged SE animals. These results demonstrated that expression patterns of hippocampal high-threshold VGCC alpha1 subunits were altered variably during prolonged convulsive SE and were associated with prominent early degenerative changes in aged neurons in CA3 and the hilus.
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PMID:Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit expression patterns after kainate-induced status epilepticus in aging rats. 1470 30

Longitudinally restricted axonal projections of hippocampal granule cells suggest that transverse segments of the granule cell layer may operate independently (the "lamellar" hypothesis). Longitudinal projections of excitatory hilar mossy cells could be viewed as antithetical to lamellar function, but only if longitudinal impulse flow effectively excites distant granule cells. We, therefore, determined the effect of focal granule cell discharges on granule cells located >2 mm along the longitudinal axis. During perforant pathway stimulation in urethane-anesthetized rats, passive diffusion of the GABA(A) receptor antagonist bicuculline methiodide from the tip of a glass recording electrode evoked granule cell discharges and c-Fos expression in granule cells, mossy cells, and inhibitory interneurons, within a approximately 400 microm radius. This focally evoked activity powerfully suppressed distant granule cell-evoked responses recorded simultaneously approximately 2.5-4.5 mm longitudinally. Three days after kainic acid-induced status epilepticus or prolonged perforant pathway stimulation, translamellar inhibition was intact in rats with <40% hilar neuron loss but was consistently abolished after extensive (>85%) hilar cell loss. Retrograde transport of Fluoro-Gold (FG) from the rostral dentate gyrus revealed that few inhibitory interneurons were among the many retrogradely labeled hilar neurons 2.5-4.5 mm longitudinally. Although many somatostatin-positive hilar interneurons effectively transported FG from the distant septum, few of these neurons transported detectable FG from much closer hippocampal injection sites. Inhibitory basket and chandelier cells also exhibited minimal longitudinal FG transport. These findings suggest that translamellar disinhibition may result from the loss of vulnerable, longitudinally projecting mossy cells and may represent a network-level mechanism underlying postinjury hippocampal dysfunction and epileptic network hyperexcitability.
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PMID:Translamellar disinhibition in the rat hippocampal dentate gyrus after seizure-induced degeneration of vulnerable hilar neurons. 1474 30


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