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)

The occurrence of seizure activity in human temporal lobe epilepsy or status epilepticus is often associated with a characteristic pattern of cell loss in the hippocampus. An experimental model that replicates this pattern of damage in normal animals by electrical stimulation of the afferent pathway to the hippocampus was developed to study changes in structure and function that occur as a result of repetitive seizures. Hippocampal granule cell seizure activity caused a persistent loss of recurrent inhibition and irreversibly damaged adjacent interneurons. Immunocytochemical staining revealed unexpectedly that gamma-aminobutyric acid (GABA)-containing neurons, thought to mediate inhibition in this region and predicted to be damaged by seizures, had survived. In contrast, there was a nearly complete loss of adjacent somatostatin-containing interneurons and mossy cells that may normally activate inhibitory neurons. These results suggest that the seizure-induced loss of a basket cell-activating system, rather than a loss of inhibitory basket cells themselves, may cause disinhibition and thereby play a role in the pathophysiology and pathology of the epileptic state.
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PMID:Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. 287 52

Suzie, a ten year old child well known on our pediatric neuroscience ward at a children's hospital in British Columbia, was admitted in August 1991 for continuing seizures and unmanageable behaviour after her fourth epilepsy surgery. She was to remain with us for a total of nine months. Very soon, it became apparent that we had an untenable situation on the ward. On the one hand, seizure control was poor and Suzie required hospitalization to adjust her medications and to treat frequent episodes of status epilepticus. On the other hand, her behaviour was seriously disruptive to other patients and staff, as well as presenting a safety concern. Negative behaviours fell into three categories--disinhibition, aggression and hyperactivity. Through slides and video tape, we will introduce Suzie and describe the progression of her disease. We will discuss, using a Nursing Case Management Model, how we took over her care, accessed community resources and eventually even accompanied her to Montreal for a right hemispherectomy. The "Suzie Experience" forced administration and staff to devise creative solutions and empowered nurses on the ward to implement new and unique strategies.
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PMID:Oh, Suzanna! A nursing challenge. 827 94

Seizures cause a persistent enhancement in dentate synaptic inhibition concurrent with, and possibly compensatory for, seizure-induced hippocampal hyperexcitability. To study this phenomenon, we evoked status epilepticus in rats with systemic kainic acid (KA), and 2 weeks later assessed granule cell inhibition with paired-pulse stimulation of the perforant path (PP) in vitro. Controls demonstrated three components of paired-pulse inhibition: early inhibition (10-30 msec), intermediate facilitation (30-120 msec), and late inhibition (120 msec to 120 sec). After seizures, inhibition in all components was enhanced significantly. The GABA(A) antagonist bicuculline blocked only early enhanced inhibition, demonstrating that both GABA(A) and GABA(B) postsynaptic receptors contribute to seizure-induced enhanced inhibition. In controls, the GABA(B) antagonist CGP 35348 increased both GABA(A) and GABA(B) responses in granule cells, suggesting that CGP 35348 acts presynaptically, blocking receptors that suppress GABA release. In contrast, slices from KA-treated rats were markedly less sensitive to CGP 35348. To test the hypothesis that GABA(B) receptors regulating GABA release are downregulated after seizures, we measured paired-pulse suppression of recurrent IPSPs, or disinhibition, using mossy fiber stimuli. Early disinhibition (< 200 msec) was reduced after seizures, whereas late disinhibition remained intact. CGP 35348 blocked the early component of disinhibition in controls and, to a lesser extent, reduced disinhibition in KA slices. However, paired monosynaptic IPSPs recorded intracellularly showed no difference in disinhibition between groups. Our findings indicate that seizure-induced enhancement in dentate inhibition is caused, at least in part, by reduced GABA(B) function in the polysynaptic recurrent inhibitory circuit, resulting in reduced disinhibition and heightened GABA release.
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PMID:Kainic acid-induced seizures enhance dentate gyrus inhibition by downregulation of GABA(B) receptors. 875 86

Traumatic brain injury (TBI) is a leading cause of symptomatic epilepsy in young adults. This study examined physiological and anatomical epileptogenic consequences of a prior incident of TBI in rats. Rats were subjected to a fluid percussion brain injury one week prior to experimentation, and in vitro electrophysiological recording studies were conducted using combined hippocampal-entorhinal cortical slices (HEC slices). Results were compared to sham operated controls and rats in which a condition of chronic temporal lobe epilepsy was induced by a 2 h bout of pilocarpine-induced status epilepticus 2 months prior to recording (PILO). In field potential recording, PILO HEC slices evidenced a greater degree of disinhibition in Ca1 than did TBI or control slices. TBI slices showed greater disinhibition in the dentate gyrus than did PILO or control rats. In in vitro kindling experiments, 86% of TBI HEC slices generated self-sustaining epileptic activity within 9 stimulus trains. This type of activity was never triggered in control slices. HEC slices prepared from PILO animals generated self-sustaining epileptic activity with fewer stimulus trains than did TBI slices. In anatomical studies, both TBI and PILO hippocampi evidenced significant loss of neurons within the hilar region. TBI induces a series of changes within the limbic system of rats, which are qualitatively similar in many aspects but quantitatively less severe than changes seen in rats with chronic temporal lobe epilepsy. These physiological and anatomical TBI-associated alterations in the limbic system may contribute to the development of epilepsy following head trauma.
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PMID:Brain injury-induced enhanced limbic epileptogenesis: anatomical and physiological parallels to an animal model of temporal lobe epilepsy. 898 90

Echographia is a phenomenon in which a patient continuously translates verbal stimuli into writing. We encountered a patient with epilepsy who developed visual echographia during interictal periods. In this case, echographia was observed during two different periods, namely the period of disturbed consciousness after the epileptic seizure and the period of clear consciousness after suppression of the seizures. Disinhibition due to disturbance of the consciousness is considered to have been the cause of echographia in the former period. In the latter period, it is considered that echographia was caused by the release of lower function from suppression of upper function by brain dysfunction, as the after effect of status epilepticus. As echographia can be observed in epileptic patients, attention and careful observation by epileptologists is needed.
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PMID:Echographia as a symptom of interictal state in an epileptic patient: a case report. 907 57

Intracellular recording techniques were used to examine GABA(A) receptor-mediated synaptic inhibition in pyramidal cells of the CA1 region of the rat hippocampus in the post-self sustaining limbic status epilepticus model of temporal lobe epilepsy. Orthodromically evoked, monosynaptic inhibitory postsynaptic potentials were recorded in vitro following pharmacological blockade of ionotropic glutamate and GABA(B) receptors. Inhibitory postsynaptic potentials from epileptic tissue were kinetically altered relative to controls; both the 10-90% rise-time and width (measured at half-maximum amplitude) were reduced by approximately 50% resulting in significant shortening of duration. The degree of pyramidal cell hyperexcitability, assessed before pharmacological treatment as the number of action potentials evoked by maximum intensity afferent stimulation, correlated significantly with the magnitude of synaptic potential duration reduction determined following blockade of glutamatergic neurotransmission. Bath application of the benzodiazepine type 1 receptor agonist zolpidem reduced post-self sustaining limbic status epilepticus CA1 pyramidal cell hyperexcitability substantially (but not completely) via a marked increase in inhibitory postsynaptic potential area. Post-self-sustaining limbic status epilepticus inhibitory postsynaptic potentials which exhibited the most pronounced shortening were augmented by zolpidem to a greater degree than longer duration synaptic potentials. In contrast, zolpidem-induced augmentation of control inhibitor, postsynaptic potential area was much less robust. It is suggested that a deficiency in post-self-sustaining limbic status epilepticus GABA(A) receptor-mediated synaptic inhibition contributes to a state of partial disinhibition which is a major factor in enhanced CA1 excitability in chronic limbic epilepsy. Possible mechanisms underlying post-self-sustaining limbic status epilepticus kinetic abnormalities are discussed.
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PMID:Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie enhanced CA1 excitability in a chronic model of temporal lobe epilepsy. 928 63

Non convulsive status epilepticus (NCSE) of frontal origin is a rare cause of mental confusion. The present case of possible frontal-onset NCSE proved to have a neuropsychological examination that was suggestive either of a disruption of attentional function or a left prefrontal dysfunction, exhibiting disturbances of immediate memory and logical programmation, perseverations and affective disinhibition. Vigilance was not impaired. This case was therefore, on a nosographic point of view, more consistent with a simple partial status epilepticus with cognitive and affective symptomatology rather than with a complex partial status epilepticus of extra-temporal origin.
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PMID:[Simple partial frontal nonconvulsive status epilepticus]. 968 10

One axiom at the basis of epilepsy research is that there exists an imbalance between excitation and inhibition. This abnormality can be achieved by an increase of excitation on principal cells, a decreased inhibition (i.e. disinhibition) or both. This review focuses on dysfunction of inhibition, and in particular on the 'dormant basket cell hypothesis'. This hypothesis states that, (1) interneurones are functionally disconnected from excitatory afferents, resulting in hyperexcitability of principal neurones and loss of paired pulse inhibition, (2) when properly activated, interneurones can still perform their task, i.e. suppress epileptiform activity and restore paired pulse inhibition. The aim of this review is to discuss the evidence in support of the 'dormant basket cell hypothesis'. We will first discuss the rationale underlying the hypothesis and the criteria needed to validate the hypothesis. We will then show that, (1) the key experimental data offered in support of the hypothesis (Bekenstein and Lothman, 1993. Dormancy of inhibitory interneurones in a model of temporal lobe epilepsy. Science 259, 97-100; Sloviter, 1991. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the 'dormant basket cell' hypothesis and its relevance to temporal lobe epilepsy. Hippocampus 1, 41-66) are difficult to interpret, and (2) recent recordings from interneurones in epileptic tissue argue against the hypothesis. The 'dormant basket cell hypothesis' is then discussed in the broader context of disinhibition.
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PMID:Interneurones are not so dormant in temporal lobe epilepsy: a critical reappraisal of the dormant basket cell hypothesis. 976 12

The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes recent work from our laboratory on the characterization of the immunocytochemical distribution of these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous distribution of immunoreactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha1, alpha2, alpha4, alpha5, beta2, beta3, gamma2, and delta. Alpha1, beta2, and gamma2 were about equally distributed in all subfields of the hippocampus; alpha4- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha2 was localized to the dentate molecular layer and CA3; alpha5 was found in the dendritic areas of CA1 to CA3; and beta1 was preferentially seen in CA2. Alpha1, beta2, gamma2 and delta were highly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactive proteins. Acute changes included decreases in alpha2, alpha5, beta1, beta3, gamma2 and delta mRNA levels (by about 25-50%), accompanied by increases (by about 50%) in alpha1, alpha4, and beta2 messages in granule cells (after 6-12 h). Chronic changes, characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha2 and beta3 subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha1, alpha2 alpha4, beta1, beta2, beta3 and gamma2 in granule cells and in the molecular layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all hippocampal subfields, may reflect altered GABA-ergic transmission during development of the epileptic syndrome. Increased expression of GABA(A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. However, the lasting preservation of alpha1-, beta2-, and gamma2-subunits in interneurons could provide a basis for augmented inhibition of GABA-ergic interneurons, leading to net disinhibition.
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PMID:Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures. 976 15

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.
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PMID:Enhanced excitability induced by ionizing radiation in the kindled rat. 1131 62


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