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)

Magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and magnetic resonance spectroscopy (MRS) were successively recorded in a 3-year-old girl with the acute hemiplegia syndrome. She was admitted to our hospital with complaints of fever, loss of consciousness and right side dominant clonic convulsions evolving into status epilepticus, and then recovered with sequelae of aphasia and right hemiparesis. Electroencephalography showed a generalized slow rhythm at the onset, and very low activities on the left hemisphere in the follow-up records. Brain CT and MRI revealed edema of the left hemisphere initially, followed by left side dominant brain atrophy. No cerebral vascular lesion was detected by magnetic resonance angiography. N-Isopropyl-[123I]-iodoamphetamine SPECT showed marked hypoperfusion of the left hemisphere accompanied by crossed cerebellar diaschisis. MRS at the initial stage detected decreased N-acetyl-aspartic acid and increased lactic acid signals in the bilateral hemisphere, which subsequently normalized only on the right side. These findings suggested brain damage and neural cell death in the left cerebral hemisphere, caused by acute encephalopathy. SPECT and MRS are useful new techniques to study the pathophysiology of the acute hemiplegia syndrome.
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PMID:[MRI, SPECT and MRS findings in a case of acute hemiplegia syndrome with a marked hemispheric brain edema]. 978 Jul 43

There is considerable controversy whether aberrant fascia dentata (FD) mossy fiber sprouting is an epiphenomena related to neuronal loss or a pathologic abnormality responsible for spontaneous limbic seizures. If mossy fiber sprouting contributes to seizures, then reorganized axon circuits should alter postsynaptic glutamate receptor properties. In the pilocarpine-status rat model, this study determined if changes in alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and n-methyl-D-aspartic acid (NMDA) receptor subunit mRNA levels correlated with mossy fiber sprouting. Sprague-Dawley rats were injected with pilocarpine (320 mg/kg; i.p.) and maintained in status epilepticus for 6 to 8 hours (pilocarpine-status). Rats were killed during the: (1) latent phase after neuronal loss but before spontaneous limbic seizures (day 11 poststatus; n = 7); (2) early seizure phase after their first seizures (day 25; n = 7); and (3) chronic seizure phase after many seizures (day 85; n = 9). Hippocampi were studied for neuron counts, inner molecular layer (IML) neo-Timm's staining, and GluR1-3 and NMDAR1-2b mRNA levels. Compared with controls, pilocarpine-status rats in the: (1) latent phase showed increased FD GluR3, NMDAR1, and NMDAR2b; greater CA4 and CA1 NMDAR1; and decreased subiculum GluR1 hybridization densities; (2) early seizure phase showed increased FD GluR3, increased CA1 NMDAR1, and decreased subiculum NMDAR2b densities; and (3) chronic seizure phase showed increased FD GluR2; increased FD and CA4 GluR3; decreased CA1 GluR2; and decreased subiculum GluR1, GluR2, NMDAR1, and NMDAR2b levels. In multivariate analyses, greater IML neo-Timm's staining: (1) positively correlated with FD GluR3 and NMDAR1 and (2) negatively correlated with CA1 and subiculum GluR1 and GluR2 mRNA levels. These results indicate that: (1) hippocampal AMPA and NMDA receptor subunit mRNA levels changed as rats progressed from the latent to chronic seizure phase and (2) certain subunit alterations correlated with mossy fiber sprouting. Our findings support the hypothesis that aberrant axon circuitry alters postsynaptic hippocampal glutamate receptor subunit stoichiometry; this may contribute to limbic epileptogenesis.
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PMID:Hippocampal AMPA and NMDA mRNA levels correlate with aberrant fascia dentata mossy fiber sprouting in the pilocarpine model of spontaneous limbic epilepsy. 985 58

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABA(A) (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABA(A) receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.
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PMID:Advances in the pathophysiology of status epilepticus. 1736 70

This study focused on the evaluation of anticonvulsant properties of isonicotinic acid benzylamide (iso-Nic-BZA) in numerous experimental seizure models (maximal electroshock [MES]-, bicuculline [BIC]-, pentylenetetrazole [PTZ]-, pilocarpine [PILO]-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA]-, kainic acid [KA]- and N-methyl-d-aspartic acid [NMDA]-induced seizures). Moreover, acute adverse-effect profile of the agent with respect to impairment of motor coordination was assessed in animals subjected to the chimney test. The evaluation of time-course and dose-response relationships for iso-Nic-BZA provided evidence that the compound produced the peak to maximum antielectroshock action and acute adverse effects at 5min after its systemic (i.p.) administration. Iso-Nic-BZA exerted a clear-cut anticonvulsant action against maximal electroshock-induced seizures in mice and its ED(50) value was 70.6 (56.4-88.4)mg/kg. The assessment of acute adverse effects in the chimney test revealed that the agent produced acute neurotoxic effects and its TD(50) value was 135.6 (108.8-169.0)mg/kg. Additionally, iso-Nic-BZA showed the anticonvulsant activity in numerous chemically-induced seizures (AMPA-, BIC-, KA-, and PTZ-evoked clonic convulsions), remaining virtually ineffective (at doses up to 200mg/kg) in PILO- and NMDA-induced seizures in mice. Based on this study, one can conclude that iso-Nic-BZA due to the short time to peak of its maximum anticonvulsant effects (5min after its i.p. administration), deserves more attention as a potential antiepileptic drug for patients in status epilepticus.
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PMID:Characterization of the anticonvulsant profile of isonicotinic acid benzylamide in various experimental seizure models in mice. 1754 62

Interrupting a focal, chronic infusion of GABA to the rat motor cortex initiates the progressive emergence of a sustained spiking electroencephalographic (EEG) activity, associated with myoclonic jerks of the corresponding body territory. This activity is maintained over several hours, has an average frequency of 1.5 Hz, is localized to the infusion site and never generalizes. The GABA withdrawal syndrome (GWS) has therefore features of partial status epilepticus. Changes in EEG signals associated with the GWS were studied in freely moving rats by measuring the phase synchrony between bilateral epidural records from the neocortex. Our results showed (i) epileptic activity was associated with a striking decrease in phase synchrony between all pairs of electrodes including the focus, predominantly in the 1-6 Hz frequency range. There was a mean decrease of 75.34+/-5.26% in phase synchrony levels between the period before GABA interruption and the period after epileptic activity appeared. (ii) This reduction in synchrony contrasted with an increase of power spectral density in the corresponding EEG channels over the same 1-6 Hz frequency range, (iii) neither changes in synchrony nor in nonlinear dynamics were detected before the first EEG spikes, (iv) systemic injection of ketamine, an antagonist of N-methyl-d-aspartic acid (NMDA) receptors, modified transiently both epileptic activity and the synchrony profile. (v) Spiking activity and synchrony changes were suppressed by reperfusion of GABA. Our data suggest that, during a partial status epilepticus, interactions between the epileptic focus and connected neocortical neuronal populations are dramatically decreased in low frequencies.
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PMID:Loss of phase synchrony in an animal model of partial status epilepticus. 1762 13

Status epilepticus (SE) describes an enduring epileptic state during which seizures are unremitting and tend to be self-perpetuating. We describe the clinical phases of generalized convulsive SE, impending SE, established SE, and subtle SE. We discuss the physiological and biochemical cascades which characterize self-sustaining SE (SSSE) in animal models. At the transition from single seizures to SSSE, GABAA (gamma-aminobutyric acid) receptors move from the synaptic membrane to the cytoplasm, where they are functionally inactive. This reduces the number of GABAA receptors available for binding GABA or GABAergic drugs, and may in part explain the development of time-dependent pharmacoresistance to benzodiazepines and the tendency of seizures to become self-sustaining. At the same time, 'spare' subunits of AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and NMDA (N-methyl-D-aspartic acid) receptors move from subsynaptic sites to the synaptic membrane, causing further hyperexcitability and possibly explaining the preserved sensitivity to NMDA blockers late in the course of SE. Maladaptive changes in neuropeptide expression occur on a slower time course, with depletion of the inhibitory peptides dynorphin, galanin, somatostatin and neuropeptide Y, and with an increased expression of the proconvulsant tachykinins, substance P and neurokinin B. Finally, SE-induced neuronal injury and epileptogenesis are briefly discussed.
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PMID:Advances in the pathophysiology of status epilepticus. 1778 31

The objective of this study was to evaluate the anticonvulsant properties of picolinic acid 2-fluoro-benzylamide (Pic-2F-BZA) in numerous experimental seizure models [maximal electroshock (MES), bicuculline (BIC), pentylenetetrazole (PTZ), pilocarpine (PILO), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainic acid (KA) and N-methyl-D-aspartic acid (NMDA)-induced seizures]. Moreover, the acute adverse-effect profile of the agent with respect to impairment of motor performance was assessed in animals subjected to the chimney test. Results indicate that Pic-2F-BZA in time- and dose-dependent manners produced both the anti-electroshock action and acute adverse effects in the MES and chimney tests in mice respectively. The experimentally derived median effective dose (ED(50) value) in the MES test was 24.2 mg/kg (at 5 min after i.p. administration), whereas the median toxic dose (TD(50) value) in the chimney test was 71.7 mg/kg. Furthermore, Pic-2F-BZA produced clear-cut antiseizure effects in all chemically induced seizure models and its ED(50) values amounted to 19.9 mg/kg for KA-, 39.5 mg/kg for AMPA-, 56.2 mg/kg for PTZ-, 76.4 mg/kg for BIC-, 160.1 mg/kg for PILO- and 165.2 mg/kg for NMDA-induced seizures. Based on this study, one can conclude that Pic-2F-BZA, because of its broad spectrum of anticonvulsant action and the short time to peak of its maximum anticonvulsant effects (5 min after its i.p. administration), deserves more attention as a potential antiepileptic drug for status epilepticus patients.
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PMID:Anticonvulsant and acute adverse effect profiles of picolinic acid 2-fluoro-benzylamide in various experimental seizure models and chimney test in mice. 1800 56

Early-life stress has been shown to destabilize the homeostatic synaptic plasticity and compromise the developing brain to the later encountered insults. This study would determine the long-term epileptogenic effect of neonatal isolation (NI) on early-life seizure. There were five groups: normal rearing (NR) rats; NI rats; NR rats suffering from status epilepticus (SE) at P12 (NR-SE); NI-SE rats; NI-SE-MK801 rats. All adult rats were video monitored to detect behavioral seizures, examined with brain magnetic resonance imaging, and assessed for hippocampal NeuN-immunoreactive (NeuN-IR) cells. Behavioral seizures were detected in one of six NR-SE rats, all the NI-SE rats (eight of eight), and none in the NR, NI, or NI-SE-MK801 rats. High hippocampal T2 signal were only found in three of five NR-SE rats, five of six NI-SE rats, and one of five NI-SE-MK801 rats. There was a significant decrease in the number of hippocampal NeuN-IR cells in the NR-SE and NI-SE groups, compared with the NR group, and MK-801 treatment ameliorated the neuronal loss. Our results demonstrated that NI led to an increase in epileptogenesis in rat pups with early-life SE, and treatment with MK-801 could ameliorate brain injuries, indicating a critical role of N-methyl-d-aspartic acid receptor in the epileptogenic process.
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PMID:Epileptogenesis is increased in rats with neonatal isolation and early-life seizure and ameliorated by MK-801: a long-term MRI and histological study. 1958 40

Status epilepticus occurring in early postnatal development protects CA1 hippocampal neurons, the region most sensitive to seizure-induced injury in the developing brain. Here, we developed a "two hit" model in dissociated cultures of the rat hippocampus to test whether pre-exposure of immature neurons to high concentrations of glutamate, N-methyl-D-aspartic acid (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) during a relatively resistant period prevents neurons from dying following a second exposure to the same chemicals after neurons mature and become highly vulnerable to excitatory amino acids (EAAs). Cultures were exposed to varied doses of glutamate, NMDA, or AMPA for 48 h at 5 DIV and again at 14 DIV for 5, 15, or 30 min. NeuN immunohistochemistry showed early exposure to glutamate (500 microM) killed approximately half of the neurons (52+/-8.6%) compared to the marked depletion that occurs after one exposure at 14 DIV (98+/-0.79%). When cultures were first challenged with moderate doses of glutamate (200 microM) followed by the high dose 7 days later, a significant population of neurons was spared (35.3+/-1.2%). Similarly, pre-exposure to maximal doses of NMDA (100 microM) increased the proportion of surviving cells following the second challenge. In contrast, AMPA (100 microM) was equally toxic after early or late applications and did not protect from the second exposure. GluR1 subunit expression was markedly decreased at 48 h after one or two exposures to 200 microM glutamate (by 44.57+/-3.6%, 45.07+/-3.69%) whereas GluR2 subunit expression was reduced by a lesser amount (25.7 57+/-3.8%). Confocal microscopy showed that one or two exposures to NMDA caused GluR2 protein to downregulate even further whereas parvalbumin (PV) was dramatically increased in the same neurons by over four-fold. On the other hand, calbindin (CB) immunoreactivity was nearly absent after the first exposure to 500 microM glutamate. These data indicate that early, transient exposure to certain EAAs at high doses can induce long-lasting neuroprotection. Alterations in the GluR1/GluR2 ratio as well as differential expression of specific calcium binding proteins may contribute to this neuroprotection.
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PMID:Early exposure of cultured hippocampal neurons to excitatory amino acids protects from later excitotoxicity. 1991 87

Status epilepticus is a clinical emergency that can lead to the development of acquired epilepsy following neuronal injury. Understanding the pathophysiological changes that occur between the injury itself and the expression of epilepsy is important in the development of new therapeutics to prevent epileptogenesis. Currently, no anti-epileptogenic agents exist; thus, the ability to treat an individual immediately after status epilepticus to prevent the ultimate development of epilepsy remains an important clinical challenge. In the Sprague-Dawley rat pilocarpine model of status epilepticus-induced acquired epilepsy, intracellular calcium has been shown to increase in hippocampal neurons during status epilepticus and remain elevated well past the duration of the injury in those animals that develop epilepsy. This study aimed to determine if such changes in calcium dynamics exist in the hippocampal culture model of status epilepticus-induced acquired epilepsy and, if so, to study whether manipulating the calcium plateau after status epilepticus would prevent epileptogenesis. The in vitro status epilepticus model resembled the in vivo model in terms of elevations in neuronal calcium concentrations that were maintained well past the duration of the injury. When used following in vitro status epilepticus, dantrolene, a ryanodine receptor inhibitor, but not the N-methyl-D-aspartic acid channel blocker MK-801 inhibited the elevations in intracellular calcium, decreased neuronal death and prevented the expression of spontaneous recurrent epileptiform discharges, the in vitro correlate of epilepsy. These findings offer potential for a novel treatment to prevent the development of epileptiform discharges following brain injuries.
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PMID:Dantrolene inhibits the calcium plateau and prevents the development of spontaneous recurrent epileptiform discharges following in vitro status epilepticus. 2059 71


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