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

1. The dentate gyrus fails to develop epileptiform activity in many experimental models of epilepsy, including the in vitro low-Ca2+ model. Although manipulating the K+ concentration or osmolality of normal low-Ca2+ perfusion mediums can enhance the propensity of the dentate gyrus to develop seizure activity, the specific mechanisms contributing to this change are still under investigation. Identification of these mechanisms should improve our understanding of epileptogenesis and of the factors contributing to the propensity for seizure discharge in other tissues. 2. In the present experiments we used externally generated electric fields to depolarize the somata of large populations of dentate granule cells during exposure to a perfusion medium with no added Ca2+ (low-Ca2+ medium). Uniform electric fields were generated across an individual slice by passing current between two parallel AgCl-coated silver wires placed on the surface of the artificial cerebral spinal fluid. The wires were positioned to straddle the slice such that the current flow was parallel to the dendrosomatic axis of the cell population under investigation. 3. Under control conditions (low-Ca2+ medium, no applied field), stimulation of the dentate hilus evoked a single antidromic population spike in 89% of the slices studied (n = 27). During application of electric fields the same stimulus evoked epileptiform activity in all trials. Well-formed bursts first occurred at an average field intensity of +22.9 +/- 2.5 (SE) mV/mm (n = 24). The amplitude of individual spikes and the total number of spikes, within a burst increased in a graded fashion as the magnitude of the applied field was increased. 4. High field intensities evoked epileptiform activity in the absence of a synchronizing antidromic stimulus. These field-induced bursts occurred after a progressive buildup of rhythmic activity recorded in the extrasomatic space and could persist for the entire duration of an applied field, lasting for several seconds. The average field intensity required to produce a threshold burst was +84.6 +/- 3.6 mV/mm (n = 24). 5. In 11% of trials (3 of 27) the dentate gyrus exhibited poorly developed antidromic bursting without the application of depolarizing electric fields. These bursts were completely suppressed by hyperpolarizing fields in the range of -10 to -20 mV/mm. 6. The results of this investigation support the hypothesis that granule cell sensitivity to nonsynaptic interactions is adequate to support bursting in a normal low-Ca2+ medium, but bursting fails to occur because these cells are normally too hyperpolarized relative to their action potential threshold.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Epileptiform activity in the dentate gyrus during low-calcium perfusion and exposure to transient electric fields. 747 40

One of the characteristic manifestations of chronic neuronal lipofuscinosis (Batten disease) is a marked predisposition for epileptic seizures. The management of these seizures is very difficult. The present study was initiated to determine what mechanisms could account for the seizure disorder. Tissue was examined from a patient with a history of Batten disease that was histologically verified. Reduced silver and Golgi impregnations were done on the parietal cortex of the patient. There was no evidence of the marked dendritic abnormalities seen in classic epileptic foci. Instead there was marked swelling and dilatation of the axon hillock and initial segment. This finding suggested that inhibition of these pyramidal neurons was markedly attenuated due to disruption of initial segment inhibitory synapses. Studies are continuing to determine if the GABA decreases seen in Batten disease may in part be due to trophic sequences brought about by loss of these critical inhibitory synapses.
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PMID:Cellular distribution of lesions in Batten disease. 766 29

We have examined the role apoptosis plays in epileptic brain damage using intra-amygdaloid injection of kainate. With the silver staining technique of Gallyas, argyrophylic (dying) neurons were observed, a few hours after the injection, in the amygdala and in the vulnerable pyramidal neurons of the hippocampal CA3 region. In both areas, cell death has apoptotic features, including: (i) nuclear chromatin condensation and marginalization with light and electron microscopy; (ii) DNA fragmentation with a typical ladder pattern on agarose gel electrophoresis; (iii) positive nuclear labelling with a selective in situ DNA fragmentation staining method. Combined in situ DNA labelling and silver staining showed that the DNA fragmentation occurred in dying neurons. CA1 or granule cells which do not degenerate following intra-amygdaloid injection of kainate were not stained with the in situ DNA labelling or the argyrophylic technique. Administration of diazepam blocked the kainate-induced seizures and prevented DNA fragmentation in CA3 but not in the amygdala. Therefore, apoptosis contributes to the local and distant damage induced by kainate.
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PMID:Kainate-induced apoptotic cell death in hippocampal neurons. 789 62

An 83-year-old female with no personal or familial neurological history developed progressive gait and speech disturbance and left motor deficit. She suffered intractable seizures and died 3 months after the onset of neurological signs. Neuropathology showed severe spongiosis and gliosis in the cortex and basal ganglia, and diffuse cerebral amyloid angiopathy. Immunostaining for prion protein (PrP) showed intense PrP positivity in areas of confluent spongiosis and some granular staining in astrocytes. The cortical vessel walls stained positively for beta/A4 amyloid but not for PrP amyloid. Both types of amyloid were only observed in pericapillary parenchyma, in areas with severe spongiosis. There were only a few tangles and neuritic plaques in the temporal cortex; amyloid plaques were not present either by silver stains or immunostains. There was neither arteriopathic leukoencephalopathy nor cerebral hemorrhage. Immunoblot analysis of brain extracts revealed an abnormal proteinase K-resistant isoform of PrP. Association of Creutzfeldt-Jakob disease and Cerebral amyloid angiopathy in the absence of Alzheimer changes in unusual. The association of PrP and beta/A4 amyloid deposits could have been fortuitous in an 83-year-old patient. An etiopathogenic relationship between beta/A4 amyloid deposition and PrP accumulation may also be considered.
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PMID:Creutzfeldt-Jakob disease and cerebral amyloid angiopathy. 794 67

Synaptic reorganization occurs in the hippocampus following various forms of seizure activity and injury, and may contribute to epileptogenesis. To address the hypothesis that neurotrophic factors play an inductive role in synaptic reorganization following seizures, we directly measured neurotrophic activity in rat hippocampal extracts after kainate injection or prolonged stimulation of the perforant path. Serial dilutions of hippocampal extracts were added to cultures of chick dorsal root ganglia, which are known to require trophic support from nerve growth factor and other neurotrophins, or ciliary ganglia neurons, which require trophic support from ciliary neurotrophic factor. Neurotrophic activity was significantly increased in hippocampal extracts harvested from 12 h to 2 months after kainate treatment, with the peak effect seen at seven days. This neurotrophic activity was substantially blocked by an anti-nerve growth factor antibody. Extracts at seven days also showed a significant increase in ciliary neurotrophic factor-like activity. Sulfide/silver histochemistry, which stains dentate granule cell axon terminals, revealed that mossy fiber sprouting was evident two weeks following kainate treatment and increased progressively over the next two to six weeks. Perforant path stimulation that produced hyperexcitability in the dentate gyrus, but no sprouting, failed to induce changes in neurotrophic activity. These results suggest there are significant increases in neurotrophic factors following kainate-induced seizures, and the increases may be related to kainate-induced hippocampal injury rather than seizures per se. Furthermore, the timecourse of increased neurotrophic activity parallels that of mossy fiber reorganization, and is consistent with the hypothesis that neurotrophic factors play a role in the injury-induced synaptic reorganization seen in epilepsy.
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PMID:Prolonged increases in neurotrophic activity associated with kainate-induced hippocampal synaptic reorganization. 825 23

Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
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PMID:Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. 835 18

Twenty cases of ECOG spike foci in epilepsy originally recorded by flaky silver electrodes on the surface of cortices and then to be removed surgically were studied under transmission electron microscope. The ultrastructural changes of the spike foci seemed to be identical in all cases although there were differences in etiologies, locations and seizure types. The presynaptic terminals of axospinal asymmetric synapses were obviously swollen anyhow, the postsynaptic spines were relatively unaffected. The synaptic vesicles were decreasing in number and to be accumulated predominantly at the presynaptic membrane which indicated that these excitatory changes of synapses may play an important role in the mechanism of epileptic abnormal electric activity and the development of epilepsy. Additionally, the ultrastructural changes and the cytopathologic significance of neurons, astrocytes and capillaries are also discussed.
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PMID:[An electron microscopic observation on spike foci of human epileptic brains]. 840 3

Severe, repetitive ("binge") ethanol intoxication in adult rats (intragastric delivery 3 times daily for 4 days in a modification of the Majchrowicz method) precipitates neuronal degeneration in selected cerebral cortical regions involved in memory and olfaction, confirming the results of Switzer and colleagues (Anat. Rec. 202: 186a, 1982). Neuronal damage was visualized with the de Olmos cupric silver technique for degenerating neurons and processes (argyrophilia), and was quantitated by total counts and densities of argyrophilic cells/fields. The specificity of the degeneration provides a neuropathological basis for the olfactory memory deficits in chronic alcoholics. In highly intoxicated rats, argyrophilia was most extensive among hippocampal dentate gyrus granule cells, pyramidal neurons in layer 3 of the entorhinal cortex, and olfactory nerve terminals in the olfactory bulb. Degenerating pyramidal neurons were also consistently seen in the insular cortex and olfactory cortical regions, such as the piriform and perirhinal cortices. There were few argyrophilic neurons in the CA regions of the hippocampus and none in the cerebellum--regions generally shown to have cell loss in long-term ethanol feeding models--but degenerating mossy fibers in the CA2 region were observed. Degeneration was maximal before the peak period of abstinence symptoms in this model, because argyrophilic densities were no greater 36 hr, compared with 8 hr after the last ethanol dose. High blood ethanol levels were required, because argyrophilia, absent from isocaloric controls, also was only evident in ethanol-intoxicated rats with mean blood ethanol levels for days 2 to 4 above 300 mg/dl; however, it increased substantially between 350 and 550 mg/dl. The resemblance of the argyrophilic distribution to the regional neuropathology that occurs in experimental seizures indicates that the ethanol-induced degeneration may have an excitotoxic basis. Progressive reductions in the seizure threshold (e.g., kindling phenomena that have been documented during binge ethanol intoxication) might be associated with excitotoxic hyperactivity during the repetitive nadirs between high blood and brain ethanol peaks. However, direct toxic actions of ethanol or its metabolites could also be involved. Overall, the model should be useful for studying mechanisms of ethanol-induced selective cortical and olfactory brain damage.
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PMID:Neuronal degeneration in rat cerebrocortical and olfactory regions during subchronic "binge" intoxication with ethanol: possible explanation for olfactory deficits in alcoholics. 873 Feb 19

The tumor suppressor gene p53 recently has been associated with the induction of cell death in response to some forms of cellular damage. A possible role for p53-related modulation of neuronal viability has been suggested by the finding that p53 expression is increased in damaged neurons in models of ischemia and epilepsy. We evaluated the possibility that p53 expression (in knockout mice) is required for induction of cell damage in a model of seizure activity normally associated with well defined patterns of cell loss. Subcutaneous injection of kainic acid, a potent excitotoxin, induced comparable seizures in both wild-type mice (+/+) and mice deficient in p53 (-/-). Using a silver impregnation technique to examine neurodegeneration in animals killed 7 d after kainate injection, we found that a majority of +/+ mice exhibited extensive cell loss in the hippocampus, involving subregions CA1, CA3, the hilus, and the subiculum. Apoptotic cell death, as identified with an in situ nick end labeling technique to detect DNA fragmentation, was confirmed in CA1- but not CA3-degenerating neurons. In marked contrast, a majority of p53 -/- mice displayed no signs of cell damage; in the remaining p53 -/- mice, damage was mild to moderate and was confined almost entirely to cells in CA3b of the dorsal hippocampus. In +/+ mice, but not in -/- mice, damaged neurons also were observed in the amygdala, piriform cortex, cerebral cortex, caudate-putamen, and thalamus after kainate treatment. The pattern and extent of damage in mice heterozygous for p53 (+/-) were identical to those seen in +/+ mice, suggesting that a single copy of p53 is sufficient to confer neuronal vulnerability. These results demonstrate that p53 influences viability in multiple neuronal subtypes and brain regions after excitotoxic insult.
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PMID:Loss of the p53 tumor suppressor gene protects neurons from kainate-induced cell death. 877 85

The case study of a schizophrenic patient with argyria which resulted from the chronic and excessive ingestion of antismoking pills contain silver, is presented. Convulsive seizures developed after the patient had been addicted to the pills for 40 years. An extremely high concentration of silver was detected in serum. This case provides support for the hypothesis that silver may cause convulsive seizures as a result of systemic poisoning.
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PMID:Argyria and convulsive seizures caused by ingestion of silver in a patient with schizophrenia. 878 81


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