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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports of glucocorticoid effects on neurotrophin expression suggest that adrenal hormones may contribute to the pattern of changes in the expression of these factors induced by neuronal activity and seizures. To examine this possibility, the present study evaluated the influence of adrenalectomy on basal expression and seizure-induced alterations in levels of nerve growth factor, brain-derived neurotrophic factor, and neurotrophin-3 messenger RNAs in hippocampus, entorhinal cortex, and superficial neocortex. For determination of hormone effects on basal expression, adult male rats were adrenalectomized and killed 10-14 days later with paired adrenal-intact controls. For studies of adrenal steroid involvement in expression following seizure, adrenalectomized and adrenal-intact rats received a seizure-producing lesion of the dentate gyrus hilus. Changes in neurotrophin messenger RNA content were assessed by quantitative in situ hybridization. Adrenalectomy alone had no significant effect on brain-derived neurotrophic factor messenger RNA content but did result in cell-specific decreases in nerve growth factor and neurotrophin-3 messenger RNAs. Nerve growth factor messenger RNA levels were reduced in hippocampal stratum granulosum, entorhinal cortex, and neocortex but not in cells of the hippocampal molecular layers or hilus. With adrenalectomy, neurotrophin-3 messenger RNA was virtually eliminated from CA2 stratum pyramidale, partially reduced in stratum granulosum, but unaffected in neurons of the hippocampal molecular layers or entorhinal cortex. These effects were partially reversed by corticosterone (2 mg/l) supplement to the drinking saline. In experimental-seizure rats, adrenalectomy did not alter the direction or basic pattern of seizure-induced changes in neurotrophin expression but did change the time courses and magnitudes of these effects. In all areas measured, brain-derived neurotrophic factor messenger RNA content was more greatly and persistently elevated by seizure in adrenalectomized as compared with adrenal-intact rats. In contrast, with adrenalectomy seizures induced smaller increases in nerve growth factor messenger RNA content. Adrenalectomy augmented the decrease in neurotrophin-3 messenger RNA induced by seizure in hippocampus but not in entorhinal cortex. These results demonstrate that adrenal hormones play a major role in the regulation of basal nerve growth factor and neurotrophin-3 messenger RNA expression by specific populations of forebrain neurons. Moreover, the adrenal steroids have opposite effects on activity-dependent changes in brain-derived neurotrophic factor and nerve growth factor messenger RNA levels but are not required for the basic pattern of changes in neurotrophin messenger RNA expression elicited by recurrent seizures.
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PMID:Cell-specific modulation of basal and seizure-induced neurotrophin expression by adrenalectomy. 747 46

Na+,K(+)-ATPase (the sodium pump) is a ubiquitous enzyme that consumes ATP to maintain an adequate neuronal transmembrane electrical potential necessary for brain function and to dissipate ionic transients. Reductions in sodium pump function augment the sensitivity of neurons to glutamate, increasing excitability and neuronal damage in vitro. Temporal lobe epilepsy (TLE) is one disease characterized by hyperexcitability and marked hippocampal neuronal losses that could depend in part, on impaired sodium pump capacity secondary to changes in sodium pump levels and/or insufficient ATP supply. To assess whether abnormalities in the sodium pump occur in this disease, we used [3H]ouabain to determine the density of Na+,K(+)-ATPase for each anatomic region of hippocampus by in vitro autoradiography. Tissues were surgically obtained from epileptic patients with hippocampal sclerosis and compared with specimens from patients with seizures originating from temporal lobe tumors and autopsy controls. Changes in cellular population arising from neuronal losses or gliosis were assessed by protein densities derived from quantitative computerized densitometry of Coomassie-stained tissue sections. We estimated regional differences in capacity for ATP generation by determining cytochrome c oxidase (CO) activity. Principal neurons of hippocampus exhibit high levels of sodium pump enzyme. Both epilepsy groups exhibited slight but significant increases in sodium pump density/unit mass of protein in the dentate molecular layer, CA2, and subiculum as compared with autopsy controls. Greater hilar sodium pump density was also observed in sclerotic hippocampi. In contrast, CO activity was reduced in both epilepsy types throughout hippocampus. Results suggest that although sodium pump protein in surviving neurons appears to be upregulated in epilepsy, sodium pump capacity may be limited by the reduced levels of CO activity. Functional reduction in sodium pump capacity may be an important factor in hyperexcitability and neuronal death.
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PMID:Regional distributions of hippocampal Na+,K(+)-ATPase, cytochrome oxidase, and total protein in temporal lobe epilepsy. 760 16

A patient is reported in whom a classic amnesic syndrome developed as a result of repeated episodes of cerebral ischaemia, accompanied by seizures. The amnesia was very severe for both old and newly acquired memories and the critical lesions defined by MRI were circumscribed areas confined to CA1 and CA2 fields of both hippocampi.
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PMID:Bilateral lesions of CA1 and CA2 fields of the hippocampus are sufficient to cause a severe amnesic syndrome in humans. 760 20

An immunoperoxidase method was used to demonstrate expression of HLA-DR (a Class II major histocompatibility antigen) as an indicator of microglial activation in cases of hippocampal sclerosis derived from temporal lobectomy for intractable seizures. HLA-DR-immunoreactive microglia were increased approximately 11-fold in CA1 and 3-fold in CA3, compared to control autopsy hippocampus. The numbers of HLA-DR-immunoreactive perivascular cells were also significantly increased in hippocampal sclerosis cases (9-, 7- and 6-fold increases in CA1, CA3 and CA2, respectively). Since animal studies have found microglial activation to be an acute or subacute response to injury, the results presented here suggest that, contrary to the classical conception of human hippocampal sclerosis as an inert scar, neuronal injury continues to occur as a result of ongoing seizure activity.
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PMID:Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy. 765 83

To clarify the origin and maintenance of epileptogenesis, morphological changes in the hippocampus of amygdaloid-kindled mice were analyzed at different stages of kindling. The granule cell size in dentate gyrus and the pyramidal cell size in CA1 were clearly decreased depending on seizure stage. The cell size in CA2 was increased and density in dentate gyrus and CA2 was reduced, significantly. The morphological changes in hippocampus associated with kindling must be closely related to the acquisition and the maintenance of epileptogenesis. The results support the hypothesis that seizure-induced damage of neurons may lead to formation of new synaptic connections that produce abnormal hyperexitability and result in seizures.
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PMID:Morphological changes in the hippocampus in amygdaloid kindled mouse. 771 56

A retrospective study was carried out to determine whether a prior cerebral injury or medical illness was associated with hippocampal sclerosis in intractable, surgically treated temporal lobe epilepsy (TLE), or whether there was evidence for progressive hippocampal neuron damage from repeated seizures. Temporal lobe epilepsy patients (n = 162) from one epilepsy centre were retrospectively and blindly catalogued into groups based on the presence or absence of an initial precipitating injury (IPI) and whether, when an IPI was present, it had involved seizures (independent variables). Patients were catalogued into four groups: (i) non-seizure IPIs (Group A; n = 54); (ii) IPIs with a prolonged seizure (Group B; n = 66); (iii) IPIs with repetitive non-prolonged seizures (Group C; n = 20); (iv) or no IPIs and idiopathic TLE (Group D; n = 22). The dependent variables were: the differences in the time course of clinical seizures, and quantified hippocampal neuron counts and seizure outcomes. Statistically significant (ANOVA at least P < 0.05) results showed the following. (i) Patients with IPIs (Groups A, B and C) had hippocampal sclerosis, while those with idiopathic TLE (Group D) showed fewer neuron losses and worse post-resection seizure relief. (ii) Patients with non-seizure IPIs (Group A) were on average older at injury; had a longer latent period; showed less neuron losses in Ammon's horn, CA1 and prosubiculum than seizure associated IPIs (Groups B and/or C). (iii) Initial precipitating injury patients with repetitive non-prolonged seizures (Group C) showed the shortest latent period, earliest age of TLE onset, and less CA2 damage than the other IPI groups. Other findings that were statistically significant by analysis of covariance along with the IPI category included the following. (i) CA1 (P = 0.0097) and prosubiculum (P = 0.0089) neuron losses were greater in patients when their TLE was longer than 22 years. (ii) IPIs after age 4 years were associated with latent periods shorter than 10 years compared with variable and longer latent periods of IPIs before age 4 years (P = 0.0015). These results indicate that in surgically treated TLE, hippocampal sclerosis and good seizure outcomes are associated with IPIs. Most of the hippocampal damage found at surgery and the clinical time course of the habitual TLE are influenced by the pathogenic IPI mechanism. However, some secondary neuron losses were associated with longer TLE seizure histories.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The clinical-pathogenic mechanisms of hippocampal neuron loss and surgical outcomes in temporal lobe epilepsy. 789 97

Surgically resected hippocampi from children with extrahippocampal seizures and structurally non-atrophic brains were examined to determine the relationship of neuron losses and aberrant mossy fiber (MF) sprouting to the postnatal migration and differentiation of the fascia dentata (FD) granule cells (GC). Percent neuron loss compared to age-matched autopsy controls was determined by quantitative cell densities, and aberrant MF sprouting by neo-Timm histochemistry. Postnatal immature GC migration and differentiation was demonstrated by the transient but GC-specific expression of the immature form of neural cell adhesion molecule (NCAM-H). Results showed that the hippocampi from children with seizures appeared microanatomically intact without focal areas of damage. However, significant neuron losses were found by neuron counts in the fascia dentata (P < 0.01), CA4 (P < 0.01), and CA2 (P < 0.05). Aberrant supragranular inner molecular layer MF sprouting was found in hippocampi of children with seizures, and the MFs showed smaller puncta in specimens resected under 2 years of age (n = 3) compared to the larger puncta in older children (n = 5). Hippocampi from children under 2 years of age also demonstrated NCAM-H positive primitive cells in the infragranular and stratum granulosum of the fascia dentata consistent with the postnatal migration and differentiation of GCs, the parent neurons of the MFs. These results indicate that seizures in the immature but structurally intact human hippocampus are associated with decreased neuron densities and aberrant MF sprouting very early in postnatal development. The data also show that aberrant MF sprouting is found during postnatal migration, differentiation and axogenesis of GCs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Children with severe epilepsy: evidence of hippocampal neuron losses and aberrant mossy fiber sprouting during postnatal granule cell migration and differentiation. 800 75

In situ hybridization was used to examine the effects of amygdala kindling on the expression of mRNAs for mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the rat hippocampus. Kindling increased MR mRNA levels in the dentate gyrus of the hippocampus 4 h after the last seizure, and these levels remained elevated 24 h later, but returned to baseline at 4 days. The only other hippocampal region that showed changes was the ipsilateral CA2 subfield where MR mRNA was significantly increased only at the 4-hour time point. Kindling also increased the levels of GR mRNA in the dentate gyrus at 4 h; however, GR mRNA levels significantly decreased below control values at 24 h before returning to normal at 4 days. These data indicate differential transient alterations in hippocampal MR and GR receptor mRNA expression following amygdala-kindled seizures.
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PMID:Modulation of hippocampal glucocorticoid and mineralocorticoid receptor mRNA expression by amygdaloid kindling. 802 20

To clarify experimentally whether benzodiazepine (Bz) receptor or regional cerebral blood flow (rCBF) imaging is more sensitive in the detection of epileptic foci, we simultaneously examined the Bz receptor and rCBF distribution changes in hippocampal kindled rabbits with in vivo double tracer autoradiography using 125I-labeled Ro 16-0154 (125I-Iomazenil) and 99mTc-labeled hexamethylpropylene amine oxime (99mTc-HMPAO). In visual and quantitative analyses, 125I-Iomazenil accumulation in brain slices extracted after the completion of the kindling was markedly and extensively decreased in the kindled right CA1 region, and further in the right temporal lobe, dentate gyrus, CA2, CA4, and bilateral CA3 regions, regarded as the propagated sites of seizure discharges. 99mTc-HMPAO accumulation was much more slightly and less extensively decreased in the right CA1, frontal, temporal and dentate gyri. Further, this decrease in 125I-Iomazenil accumulation was not due to neuropathological abnormalities, which consisted only of tissue damage corresponding to electrode track in the CA1. Both the kindled and propagated sites are known to have a possibility of acquiring epileptogenesis as experimental epileptic foci. These results suggest that Bz receptor imaging is much more sensitive in the detection of epileptic foci than rCBF imaging, and therefore that Bz receptor imaging is useful in clinical epilepsy.
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PMID:Comparison of benzodiazepine receptor and regional cerebral blood flow imaging of epileptiform foci in hippocampal kindled rabbits: a study with in vivo double tracer autoradiography using 125I-iomazenil and 99mTc-HMPAO. 803 93

In order to assess the role of neuronal activity in the regulation of the fibroblast growth factor system, we examined changes in levels of basic fibroblast growth factor and the expression of its receptor-1 following seizures. Epileptiform activity was induced by kainate injection and the rats displaying seizures were killed 3, 6, 12 and 24 h after injection. To identify basic fibroblast growth factor and fibroblast growth factor receptor-1 immunoreactivity, we used a monoclonal antibody that binds to the biological active form of basic fibroblast growth factor and a monoclonal antibody that recognizes fibroblast growth factor receptor-1. In normal brain tissue, fibroblast growth factor staining was widely distributed throughout the brain and appeared to be localized within the nucleus of astrocytes. Starting 6 h after seizures, there was a progressive increase in basic fibroblast growth factor immunoreactivity. The seizure-induced effect on basic fibroblast growth factor immunoreactivity was expressed in astrocytes as an enlargement of the nucleus and a spreading of the staining to the processes. This phenomenon was particularly strong in the cerebral cortex and hippocampus. The fibroblast growth factor receptor-1 immunoreactivity was virtually absent in control brain tissue. By 3 h post-seizure induction, there was an increase in fibroblast growth factor receptor-1 immunoreactivity in the molecular layer of the dentate gyrus. After 6 h, fibroblast growth factor receptor-1-positive cells appeared in the stratum oriens along the CA1, CA2 and CA3 hippocampal subfields. This effect gradually expanded to other brain regions and by 24 h fibroblast growth factor receptor-1 immunoreactivity was distributed throughout the hippocampus and cerebral cortex. Fluorescent double labelling indicated that the fibroblast growth factor receptor-1 immunoreactivity was expressed in astrocytes. At 24 h, some fibroblast growth factor receptor-1 immunoreactivity was also observed in neuron-like cells located throughout the cerebral cortex and hippocampus. Since our results indicate that seizure activity modulates the expression of basic fibroblast growth factor and fibroblast growth factor receptor-1 levels, it is also possible that physiological stimulation might have similar effects. In addition, our results suggest that the fibroblast growth factor system may have a role in plasticity events triggered by physiological activity.
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PMID:Seizure-associated induction of basic fibroblast growth factor and its receptor in the rat brain. 807 86


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