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

The FVB mouse is used extensively in transgenic research because of its defined inbred background, superior reproductive performance, and prominent pronuclei, which facilitate microinjection of genomic material. Seizures associated with a known mutation and seizure-susceptible inbred strains are well documented in mice; however, to the authors' knowledge, seizures in the FVB strain have not been evaluated. Affected nonmanipulated FVB/N (n = 5) and transgenic FVB/N mice generated, using eight unrelated transgenic constructs (n = 63), were submitted for pathologic examination. Most cases were detected during routine observations in animal rooms; however, seizure induction by tail tattooing, fur clipping, and fire alarms has been observed. The majority of mice were female (62 of 68), with mean age of 5.8 months (range, 2 to 16 months). Observations made during seizure presentation in 12 of 68 mice included facial grimace, chewing automatism, ptyalism with matting of the fur of the ventral aspect of the neck and/or forelimbs, and clonic convulsions that frequently progressed to tonic convulsions and death. Four mice were dead at presentation, with matting of the fur of the neck and forelimbs. The remainder of the mice had nonspecific signs of disease, such as lethargy, moribundity, or matting of the fur. Vendor and in-house animal health surveillance reports indicated that mice were seronegative to all murine pathogens. Results of gross pathologic examination were unremarkable. Microscopic findings were limited to the brain and liver. In all mice, neuronal necrosis was present in the cerebral cortex, hippocampus, and thalamus. Concurrent astrocyte hypertrophy, as evidenced by an increase in glial fibrillary acidic protein staining, was detected. Acute coagulative necrosis of centrilobular hepatocytes was present in the liver of some cases (19 of 68). Infective agents were not detected in selected brain specimens submitted for electron microscopy or in brain and liver specimens evaluated by use of special stains. Cytopathologic effect was not observed in 3T3, Vero, and BHK-21 cell lines inoculated with brain and liver specimens. The ischemic neuronal necrosis observed in these mice is consistent with lesions associated with status epilepticus in humans. The hepatocellular changes are interpreted to be agonal and associated with terminal hypoxia in seizuring animals. These results provide evidence of a previously unrecognized, often lethal epileptic syndrome in FVB mice that may have a major impact on transgenic research and other disciplines using this mouse strain.
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PMID:Neuropathologic findings associated with seizures in FVB mice. 951 87

High-affinity uptake of glutamate from the synaptic cleft plays a crucial role in regulating neuronal activity in physiological and pathological conditions. We have used affinity-purified specific polyclonal antibodies raised against a synthetic peptide corresponding to the C-terminal region of rabbit and rat EAAC1, a glutamate (Glu) transporter believed to be exclusively neuronal, to investigate its cellular and subcellular localization and whether it is expressed exclusively in glutamatergic cells of infragranular layers, as suggested by previous studies. Light microscopic studies revealed that EAAC1 immunoreactivity (ir) is localized to neurons and punctate elements in the neuropil. EAAC1-positive neurons were more numerous in layers II-III and V-VI, i.e. throughout all projection layers. Most EAAC1-positive neurons were pyramidal, although nonpyramidal cells were also observed. Some EAAC1-positive non-pyramidal neurons stained positively with an antiserum to GAD, thus demonstrating that EAAC1 is not confined to glutamatergic neurons. Non-neuronal EAAC1-positive cells were also observed in the white matter, and some of them stained positively with an antiserum to GFAP. Ultrastructural studies showed that EAAC1-ir was in neuronal cell bodies, dendrites and dendritic spines, but not in axon terminals, i.e. exclusively postsynaptic. Analysis of the type of axon terminals synapsing on EAAC1-ir profiles showed that 97% of them formed asymmetric contacts, thus indicating that EAAC1 is located at the very sites of excitatory amino acid release. Unexpectedly, EAAC1-ir was also found in a few astrocytic processes located in both the gray and the white matter. The localization of EAAC1 may explain the pathological symptoms that follow EAAC knockout (seizures and mild toxicity), as seizures could be due to the loss of EAAC1-mediated fine regulation of neuronal excitability at axodendritic and axospinous synapses, whereas the mild toxicity may be related to the functional inactivation of astrocytic EAAC1.
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PMID:EAAC1, a high-affinity glutamate tranporter, is localized to astrocytes and gabaergic neurons besides pyramidal cells in the rat cerebral cortex. 954 90

Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.
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PMID:Nerve gas-induced seizures: role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex. 957 Aug 17

Dysembryoplastic neuroepithelial tumor (DNT) is a relatively new neuroepithelial neoplasm that was first described by Daumas-Duport et al. in 1988. It was incorporated in the revised World Health Organization classification of brain tumors in 1993. The authors present the first case of DNT reported in the Latin-American literature. A 16-year-old woman had been found at age of five years to have complex partial seizures accompanied by secondary generalization. She was treated with various anti-epileptic drugs but always with incomplete control of seizures activity. Neurological examination was normal. Magnetic resonance imaging demonstrated a lesion in the left temporal lobe. She underwent a craniotomy with complete resection of the tumor. Histological study showed atypical neuroglial proliferation characteristic of DNT. Monoclonal antibody immunostaining for glial fibrillary acidic protein and S-100 protein confirmed the glial component, and neuronal specific enolase and synaptophysin emphasized the neuronal component.
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PMID:[Dysembryoplastic neuroepithelial tumor. Case report]. 962 69

We report a case of a 15-year-old girl with new onset seizures, who had a mixed dysembryoplastic neuroepithelial tumor (DNT) and ganglioglioma of the right parieto-occipital lobe. The tumor appeared well demarcated and exhibited a low T1 and a high T2 signal on magnetic resonance imaging. Architecturally it was in large part intracortical and multinodular, but also featured a leptomeningeal component. The former corresponded to DNT, a proliferation of oligodendroglia-like cells (OLCs) arranged in nodules, as well as comprising a diffuse internodular element featuring "floating neurons" in a mucoid matrix. The leptomeningeal portion of the lesion was a ganglioglioma consisting of large neurons and astrocytes in association with marked desmoplasia. Spatially, the two components abutted one another but appeared distinct. Immunohistochemistry showed the neurons of the ganglioglioma to be positive for class III beta-tubulin, synaptophysin, and chromogranin A, whereas the astrocytic cells stained only for glial fibrillary acidic protein. Most OLCs in the DNT were positive for S-100 protein. This apparently mixed lesion suggests that a close histogenetic relationship exists between DNT and ganglioglioma. We postulate that the pluripotential progenitor cells residing in the subpial granular layer may have given rise to the cortical DNT and to the leptomeningeal ganglioglioma. To our knowledge, this is the first detailed histological, immunochemical and ultrastructural report of a mixed DNT and ganglioglioma.
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PMID:Mixed dysembryoplastic neuroepithelial tumor and ganglioglioma. 965 Jul 58

This work has explored the relationship between excitotoxicity and the amyloid precursor protein gene (APP) which may be relevant to future therapeutic developments in Alzheimer's disease. The excitotoxic effects of kainic acid (KA) and pentylenetetrazole (PTZ) have been compared and contrasted on the two major mRNA isoforms of APP using in situ hybridization and quantitative analysis of gene expression in rat brain. The Kunitz Protease Inhibitor containing isoform APP 770 KPI+, the major glial cell isoform, has been shown to be stimulated after KA and was related to neuronal loss and astrocyte activation as gauged by GFAP mRNA. This was associated with reduced expression of APP695 KPI- isoform, the major neuronal isoform. These changes were not observed after PTZ where there was no neuronal loss and no glial reaction. The KA induced changes in APP were prevented by pretreatment with the non-competitive NMDA receptor antagonist dizocilpine and the barbiturate pentobarbitone, but not with the kappa-opioid receptor agonist enadoline. These findings were related to the suppression of seizures and the survival of neurons. In conclusion, excitotoxic stimulation leading to neuronal death was associated with increased expression of APP KPI+ mRNA and decreased APP KPI- mRNA, a finding which may relate to the plasticity of the central nervous system.
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PMID:The effects of excitotoxicity on the expression of the amyloid precursor protein gene in the brain and its modulation by neuroprotective agents. 972 Sep 74

We studied physiological properties of glial cells from acute slices of biopsies from patients operated for intractable mesio-temporal lobe epilepsy using whole-cell patch-clamp recordings. Cells were filled with Lucifer Yellow (LY) during recordings to allow morphological reconstruction and immunohistochemical cell identification. Seizure-associated astrocytes had complex, arborized, highly branched processes giving them a stellate appearance, and cells stained intensely for the intermediate filament GFAP as previously reported for 'reactive' astrocytes. GFAP-positive astrocytes from epilepsy biopsies consistently expressed voltage-activated, TTX-sensitive Na+ channels that showed fast activation and inactivation kinetics. Unlike comparison astrocytes, derived from tissues that were not associated with seizure foci, these astrocytes expressed Na+ channels at densities sufficient to generate slow action potentials (spikes) in current clamp studies. In these cells, the ratio of Na+ to K+ conductance was consistently 3-4-fold higher than in comparison human or control rat astrocytes. Four of 17 astrocytes from epilepsy patients versus 14/14 from control rat hippocampus and four of five in comparison human tissue showed a lack of inwardly rectifying K+ currents, which in normal astrocytes are implicated in the control of extracellular K+ levels. These results suggest that astrocytes surrounding seizure foci differ in morphological and physiological properties, and that glial K+ buffering could be impaired at the seizure focus, thus contributing to the pathophysiology of seizures.
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PMID:Properties of human glial cells associated with epileptic seizure foci. 976 28

The effects of GM1 monosialoganglioside pretreatment on brain damage resulting from soman-induced seizure activity were examined in this study. Male Sprague-Dawley rats were infused with GM1 via an osmotic minipump connected through a permanent cannula implanted intracerebroventricularly and challenged with soman (83 micrograms/kg, i.e., 1.25 x LD50) 4 d after initiation of GM1 infusion. Electrocorticographic recordings were monitored via indwelling cortical electrodes. Twenty-seven hours after soman administration, anesthetized rats were euthanized via transcardial perfusion with buffered paraformaldehyde. Brains were processed for hematoxylin and eosin (H&E), cresyl violet (CV), and acetylcholinesterase (AChE) histochemistry, and glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) immunohistochemistry. All soman-challenged rats not infused with GM1 (n = 14) developed status epilepticus (SE).
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PMID:GM1 monosialoganglioside pretreatment protects against soman-induced seizure-related brain damage. 977 43

Dysembryoplastic neuroepithelial tumor (DNT) is a recently described rare brain neoplasm with characteristic clinical and morphological features and favorable prognosis. We report here two cases of DNT. The first concerned a 12 years old girl who presented complex seizures preceded by acoustic aura (melodies). Computed tomography revealed a hypodense tumor measuring 2 x 2.5 cm in diameter, located paracortically in the left temporal lobe. The second tumor was removed from a 21-year-old man with partial complex seizures. Nine years earlier patient underwent neurosurgery with partial removal of the tumor The tumor's histopathologic diagnosis is unfortunately lacking. Computed and magnetic resonance imaging showed a mass occupying the cortex and paracortical areas of the anterior pole of the temporal lobe. Histologically, both tumors consisted of small, S-100 protein immunopositive oligodendrocyte-like cells (OLCs) arranged between synaptophysin- and, to a lesser degree, NFP-immunopositive axons (glioneuronal element). In the second case, an area of pilocytic astrocytoma-like appearance was also found, these cells were immunopositive for GFAP. The present study provides clinical, radiological and histological data, which may be helpful in differential diagnosis of this newly recognised brain tumor.
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PMID:Clinical, radiological and histological presentations of dysembryoplastic neuroepithelial tumors (DNT). Report of two cases. 981 23

Extracellular matrix proteins are induced by activity in adult brain but the time course of these responses, and hence the possibility of their involvement in use-dependent synaptic plasticity, is not known. To evaluate this issue, the influence of seizures on fibronectin expression was evaluated in the adult and developing hippocampus. In adult rats, kainic acid-induced seizures increased fibronectin mRNA and immunoreactivity (ir) by about 1 h after the first behavioral seizure. In situ hybridization analysis indicated that fibronectin mRNA was increased in broadly distributed glial cells as well as within discrete neuronal populations that normally express this transcript. Western blots demonstrated that increased fibronectin-ir was evident in both soluble and non-soluble fractions at the same time point. Immunocytochemical colocalization confirmed that fibronectin-ir was indeed elevated in broadly distributed glial fibrillary acidic protein-ir astroglia. Seizures had no detectable effect on fibronectin-ir in the hippocampus of nine day old rats. Together with previous results, the above findings suggest that intense physiological activity triggers a 'matrix response' (i.e., release proteases, activate integrins, secrete matrix proteins) that is sufficiently rapid to participate in the consolidation of long-term potentiation (LTP). The absence of such reactions in the immature hippocampus is in accord with the hypothesis that matrix proteins generated by mature astroglia impose temporal and spatial limitations on axonal remodeling.
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PMID:Seizure induced synthesis of fibronectin is rapid and age dependent: implications for long-term potentiation and sprouting. 981 31


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