Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

The effects of repeated electroconvulsive shock (ECS) and/or lidocaine treatment in the rat were studied by means of biochemical markers: GFAP (glial fibrillary acidic protein), NCAM (neural cell adhesion molecule), NSE (neuron specific enolase) and D3-protein. In adult rats given daily either ECS alone or in combination with lidocaine (experiment 1) we found that ECS significantly increased the concentration of the glial marker GFAP in limbic areas: hippocampus, amygdala, and piriform cortex. The maximal increase in GFAP was found in the piriform cortex (77%). In both piriform cortex and amygdala ECS also induced a significant decrease in D3-protein (a marker of mature synapses), but no change in NCAM (especially enriched in newly formed synapses). In piriform cortex the ratio between NCAM and D3-protein was significantly increased (4%) by ECS. The lidocaine treatment, which induced seizures in some of the animals, was without significant effect on the biochemical markers. However, multiple lidocaine-induced seizures (experiment 2) were found to be associated with a significant increase in GFAP in amygdala and piriform cortex. The study shows that seizures, whether electrically or pharmacologically induced, activate astrocytes in certain brain regions. This activation is especially pronounced in the piriform cortex and may be caused by a particularly marked synaptic vulnerability and remodeling in this area, as demonstrated by the increased NCAM/D3-ratio. Synaptic remodeling and activation of astrocytes may well influence brain function and could play a role in the chain of neurobiological events underlying the clinical effects of electroconvulsive therapy (ECT).
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PMID:Electroconvulsive shock and lidocaine-induced seizures in the rat activate astrocytes as measured by glial fibrillary acidic protein. 837 17

Limbic seizures induce in vulnerable structures, such as the hippocampal complex, morphologic changes that may contribute to the development of epilepsy. They include neuronal cell death, reactive gliosis, and neosynapse formation. In temporal lobe epilepsy patients, cell death develops in Ammon's horn and the hilus. This cell death involves both necrotic and apoptotic mechanisms and is likely responsible for the initiation of the glial reaction that consists of astroglial and macrophage proliferation and hypertrophy. Reactive astrocytes acquire the phenotypic properties of type 2 astrocytes and express trophic factors (e.g., bFGF), cell adhesion molecules (e.g., NCAM), and substrate molecules (e.g., tenascin-C). Seizures induce in the hippocampus a synaptic remodeling of mossy fibers. Mossy fiber collaterals innervate granule cell dendrites, creating recurrent excitatory circuits. We suggest that collateral branches of MF originate under the influence of trophic factors and as a consequence of an overproduction of tubulin polymers. In fact, seizures induce a transient increased expression of tubulin and microtubule-associated proteins in granule cells and mossy fibers. Navigation of mossy fiber growth cones may be facilitated by the interaction with astrocytes, which would exert this effect by producing and excreting cell adhesion and substrate molecules. In light of the results discussed here, one can suggest that in the adult brain, activated astrocytes could contribute to the process of axonal outgrowth and synaptogenesis.
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PMID:Molecular and cellular cascades in seizure-induced neosynapse formation. 899 81

Immunoreactive highly polysialylated neural cell adhesion molecule (PSA-NCAM) expression was examined in the rat with repeated exposure to amygdaloid kindled generalized seizures (GS). In the sham control brain, PSA-NCAM staining was slightly observed in the subventricular zone (SVZ) of the striatum. The number of PSA-NCAM positive cells increased four times in the bilateral SVZ after three consecutive GS, with a further increase after 30 consecutive GS. As PSA-NCAM is involved in neural plasticity as well as migration of neural stem cells (NSC), expression of PSA-NCAM in the SVZ suggests that the recurrent GS may mainly contribute to reconstruction of synaptic network and could also contribute to NSC migration after kindling.
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PMID:Expression of highly polysialylated neural cell adhesion molecule in rat subventricular zone with exposure to repeated kindled seizures. 1195 29

Highly polysialylated neural cell adhesion molecules (PSA-NCAMs) are involved in migration of neural stem cells as well as neural plasticity. Immunoreactive PSA-NCAM expression was examined in rat with repeated exposure to amygdaloid kindled generalized seizures (GS). The number of PSA-NCAM positive cells in bilateral dentate gyrus (DG) increased significantly at GS. Although total positive cell number was not significantly different between 3 times GS (3 GS) and 30 times GS (30 GS) groups, a greater number of positive cells was located in the outer granule cell layer (GCL), and the immunopositive dendrite greatly extended to the molecular layer in the 30 GS group. These observations indicate that increased migration of newly generated cells as well as plastic change of originally-existed neural cells may occur in response to the recurrent GS, which may contribute to abnormal reconstruction of synaptic network in hippocampus and epileptogenisity in kindling.
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PMID:Changes of localization of highly polysialylated neural cell adhesion molecule (PSA-NCAM) in rat hippocampus with exposure to repeated kindled seizures. 1213 37

Impairment of GABA-mediated inhibition is one of the main hypotheses invoked to explain seizure activity, both in experimental models and in human epilepsy. We have studied the distribution and the neurochemical characteristics of certain GABAergic circuits in the normal and epileptic human sclerotic hippocampal formation. We have focused our attention mainly on chandelier cells because, together with basket cells, they are considered to have powerful effects on spike generation. Chandelier cells represent a unique type of interneuron whose axon terminals (Ch-terminals) form synapses with the axon initial segments of cortical pyramidal cells and granular cells of the dentate gyrus. Different neurochemical subpopulations of chandelier cells have been identified by immunocytochemistry, mainly in the neocortex. Markers for Ch-terminals include the GABA transporter 1 (GAT-1), the polysialylated form of the cell-surface glycoprotein neural cell adhesion molecule (PSA-NCAM) and the calcium-binding proteins parvalbumin (PV) and calbindin D-28k (CB). In the normal hippocampal formation, GAT-1- and PV-immunoreactive (-ir) Ch-terminals were identified in the granular and polymorphic layers of the dentate gyrus, in the strata pyramidale and oriens of the CA fields, and in the pyramidal layer of the subicular complex. In addition, and in contrast to the hippocampus and dentate gyrus, subsets of Ch-terminals in the upper pyramidal layer of the normal subiculum express CB and PSA-NCAM. The sclerotic hippocampus of epileptic patients presented an impressive morphological and neurochemical reorganization of Ch-terminals and basket formations. This was apparent in the dentate gyrus and hippocampal formation, but not in the subiculum, which appeared to remain unaltered. Principally, numerous and more complex PV- and CB-ir Ch-terminals, as well as dense PV-ir basket formations, appeared in some hippocampal segments, whereas in other regions there was a lack of labelled elements. These changes varied considerably not only between different patients, but also within different hippocampal fields in a given patient. In general, the changes were not correlated with the clinical characteristics or degree of histopathological alterations observed in the patients, such as granular cell dispersion, neuron loss and proliferation of mossy fibres. However, some surviving neurons in the regions adjacent to the areas of neuron loss were consistently innervated by dense basket formations and complex Ch-terminals. These results indicate that, in the human epileptic hippocampus, GABAergic circuits are more highly modified than previously thought. When considered along with other extrahippocampal alterations, we suggest that these changes are important in the pathophysiology of temporal lobe epilepsy associated with hippocampal sclerosis.
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PMID:Histopathology and reorganization of chandelier cells in the human epileptic sclerotic hippocampus. 1453 59

The highly polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in migration of neural stem cells as well as in neural plasticity. Immunoreactive PSA-NCAM expression was examined in rats with repeated exposure to amygdaloid kindled generalized seizures (GS). The number of PSA-NCAM positive cells in the bilateral dentate gyrus (DG) increased significantly from GS. Although the total number of positive cells was not significantly different between animals with 3 times GS (3 GS) and 30 times GS (30 GS), in the latter group a greater number of positive cells was observed in the outer granule cell layer (GCL) and a marked extension of immunopositive dendrites to the molecular layer. These observations indicate that increased migration of newly generated cells as well as plastic changes of preexisting neural cells occur in response to recurrent GS. This may contribute to an abnormal reconstruction of the synaptic network in the hippocampus and, thus, epileptogenicity from kindling.
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PMID:Highly polysialylated neural cell adhesion molecule (PSA-NCAM) positive cells are increased and change localization in rat hippocampus by exposure to repeated kindled seizures. 1475 9

There is an increase in the birth of dentate granule neurons after status epilepticus (SE) and there are concurrent alterations in neurotransmitter receptor expression that may contribute to the development of spontaneous seizures. To determine whether newborn and/or mature dentate granule neurons have altered neurotransmitter receptor expression after SE, we dissected individual immature, PSA-NCAM-expressing, or mature, NeuN-expressing, dentate granule neurons 2 weeks after lithium-pilocarpine-induced SE in postnatal day 20 rats. Amplified single-cell RNA was used to probe reverse Northern blots containing alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate neurotransmitter receptor subunits. Two weeks after lithium-pilocarpine-induced SE there were increases in AMPA GluR2 and kainate KA2 subunit mRNA and decreases in AMPA GluR3 and kainate GluR6 receptor subunit mRNA levels in mature dentate granule neurons. In contrast, only the kainate GluR6 subunit expression was reduced in immature dentate granule neurons after SE. Alterations in transcription of excitatory amino acid receptor subunits after SE occur primarily in the mature population of dentate granule neurons. Our findings suggest that neurotransmitter receptor gene expression is altered differently in immature and mature dentate granule neurons following SE, and may result in differential contributions of these two groups of dentate granule neurons to the subsequent development of epilepsy.
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PMID:Status epilepticus differentially alters AMPA and kainate receptor subunit expression in mature and immature dentate granule neurons. 1681 74

The neural cell adhesion molecule NCAM and its dynamically regulated posttranslational modification polysialic acid (PSA) are major determinants of cellular interactions during ontogeny. While NCAM in the absence of PSA stabilizes cell-cell interactions, the attachment of the large and polyanionic PSA negatively influences cell adhesion and promotes plasticity. Disease-associated changes in the polysialylation state of NCAM raise the question whether the PSA-NCAM system can affect CNS pharmacology. Here we investigated the pharmacological effects of the competitive AMPA antagonist NBQX in genetic mouse models either lacking NCAM and PSA (female NCAM knockout mice) or being drastically reduced in the level of PSA expression (female ST8SiaIV knockout mice). Studies were carried out with the respective wildtype littermate controls. In mice lacking NCAM and PSA, NBQX-induced ataxia proved to be more intense as compared with wild-type mice. On both mutant backgrounds, NBQX significantly elevated seizure thresholds during i.v. infusion of the chemoconvulsant pentylenetetrazole. In summary, the data demonstrate that the PSA-NCAM system impacts AMPA receptor pharmacology under in vivo conditions. The fact that comparable effects were observed in NCAM- and ST8SiaIV-knockout mice indicates that this impact is not due to a stabilizing effect of NCAM in the absence of PSA. Thus, disease-related changes in the polysialylation of NCAM are likely to be associated with effects on the efficacy and tolerability of AMPA receptor antagonists.
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PMID:Deficiency of neural cell adhesion molecule or its polysialylation modulates pharmacological effects of the AMPA receptor antagonist NBQX. 1832 13

The article describes a case of a 15-year old boy after a head contusion with a five-month history of headaches and two seizure episodes. MR imaging revealed a partly solid and partly cystic cortical-subcortical tumour within the precentral gyrus with post-contrast enhancement. The patient underwent gross total resection of the lesion. Histologically the neoplasm was composed of pseudopapillary gliovascular structures surrounded by solid glioneuronal tumour areas. The expression of GFAP and nestin characterized the central parts of the tumour. Moreover the immunolabelling for synaptophysin, neurofilaments, Olig2 and NCAM was present in the peripheral part of the lesion. The neoplasm was consistent with a papillary glioneuronal tumour - one of the new entities in the last WHO CNS tumour classification.
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PMID:Papillary glioneuronal tumour of the precentral gyrus. 1858 11


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