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

Neuroanatomical methods have been used to study selective vulnerability after global brain ischemia. A consistent pattern of ischemic neuronal damage is found in the rodent hippocampus with loss of CA1 neurons and of some cells in the hilus of the dentate gyrus. Very little is known about plastic changes that would be expected in ischemia-resistant areas such as CA3 neurons and granule cells. Neuronal plasticity after lesions may be indicated by changes in labeling with antibodies to the growth-associated protein 43 (GAP-43). Expression of GAP-43 as a marker for neuronal plasticity was studied here in the hippocampus after global brain ischemia. Halothane-anesthetized rats were subjected to 20 min of transient forebrain ischemia using four-vessel occlusion. In situ hybridization was used to study GAP-43 mRNA at 1, 3, 6, and 12 h and at 1, 3, and 7 days after ischemia. Immunostaining was carried out with two different antibodies to GAP-43 in brains which were perfusion-fixed after 1, 2, 4, and 7/8 days. In the control hippocampus, GAP-43 mRNA was localized to CA1-CA3 and the hilus. Moderate increases in cellular signals were seen in hilar cells and granule cells early after ischemia, and some changes occurred in CA3 at late stages. Hybridization was lost in CA1 due to cell death. With immunostaining, GAP-43 was not seen in the cytoplasm of neurons, whereas dense labeling occurred in a differentiated pattern in the axonal and dendritic layers. At 1 day after ischemia, neurons in the hilus of the dentate gyrus and in the stratum pyramidale and lucidum of CA3 showed strong cytoplasmic labeling for GAP-43. Few cells were labeled in these regions at 2 days, and none at later stages. Pyramidal cells in CA1 and CA3 areas and granule cells were never labeled. These studies demonstrate a transient expression of GAP-43 mRNA and protein in a subset of vulnerable neurons after transient brain ischemia. The cytoplasmic localization in hilar neurons could be due to increased synthesis of GAP-43 or to changes in axoplasmic transport. It is suggested that axonal damage occurs in hilar cells which stimulates GAP-43 expression. The increased production of trophic factors after ischemia in granule cells could also cause plastic changes in hilar cells. Since hilar neurons are in a strategic position to control the excitability of the dentate area, increased expression of GAP-43 may indicate an important pathophysiological process. In seizure experiments, strong expression of GAP-43 mRNA in granule cells was associated with abnormal mossy fiber sprouting and development of chronic epilepsy. The relevance of the minor GAP-43 mRNA upregulation after ischemia must be considered. The changes in CA3 neurons at several days after ischemia might represent a plastic response to a loss of CA1 neurons.
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PMID:Transient expression of GAP-43 within the hippocampus after global brain ischemia in rat. 908 58

In human temporal lobe epilepsy, seizures can begin in the hippocampus, amygdala, or surrounding cortical areas. Histologically, the seizure-induced selective neuronal damage and synaptic reorganization are best documented in the hippocampus. Little information is available about the damage in the other temporal lobe structures or whether the distribution of damage depends on the location of the primary seizure focus. We used an amygdala-kindling model of temporal lobe epilepsy to study whether seizures of amygdaloid origin cause damage to the amygdala and hippocampus. All rats experienced five class 5 generalized seizures. Neuronal damage was assessed by counting the density of GABA-immunoreactive (GABA-ir) and somatostatin-immunoreactive (SOM-ir) neurons in the amygdala and hilus of the dentate gyrus six months after the last seizure. We found that the density of GABA-ir neurons did not differ from that in controls in the contralateral amygdala. The density of SOM-ir neurons was, however, decreased in the lateral (69% of neurons remaining, P < 0.01), basal (67% remaining, P < 0.05), and accessory basal (68% remaining, P < 0.05) nuclei. In the hilus, the densities of GABA-ir and SOM-ir neurons were similar to that in controls. According to our data, a few seizures of amygdaloid origin may cause more severe damage to SOM-ir neurons in the amygdala than in the hilus. Such decrease in SOM-ir neurons which form one subpopulation of GABAergic inhibitory interneurons may increase the local excitability in the amygdala and, therefore, contribute to epileptogenesis.
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PMID:Decrease in somatostatin-immunoreactive neurons in the rat amygdaloid complex in a kindling model of temporal lobe epilepsy. 909 93

Deep prepiriform cortex has an important role in modulating neurotransmission during limbic seizures. We used pharmacologic blockade of non-N-methyl-D-aspartate (NMDA) receptors to study excitatory circuitry from the deep prepiriform cortex to the hippocampus during global ischemia in rat. NBQX, a potent non-NMDA glutamate receptor antagonist, was microinjected stereotactically into the deep prepiriform cortex before global ischemia for 10 min. Neuronal cell death in the hippocampus was evaluated quantitatively 72 h after ischemia. The NBQX-injected rats had a greater number of surviving cells in CA1 sector of hippocampus than did saline-injected controls or rats that received NBQX injections 1 mm from the target. Thus, excitatory amino acid-mediated circuitry emanating from deep prepiriform cortex modulates ischemic neuronal injury in the hippocampus.
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PMID:Deep prepiriform cortex modulates neuronal cell death in global ischemia. 911 8

We investigated in vivo the expression of the tissue inhibitor of metalloproteinases-1 (TIMP-1) in the rat CNS after kainate (KA)-induced excitotoxic seizures. In situ hybridization revealed that TIMP-1 mRNA is induced rapidly and massively in most regions of the adult forebrain after KA treatment. Neuronal activity seems to be necessary but not sufficient to trigger TIMP-1 induction, because it is not observed in seizing 10-d-old pups, unlike what is observed in 21- and 35-d-old animals after seizures. The rapid induction of TIMP-1 is not prevented by the inhibitor of protein synthesis cycloheximide, suggesting that, after seizures, TIMP-1 is induced in neurons as an immediate early gene (IEG). The initial neuronal upregulation is followed by enhanced expression in astrocytes, as assessed by double-labeling experiments. In the hippocampus rapid increases in mRNA are followed by relatively delayed (8 hr after KA) increases in TIMP-1 immunoreactivity in the perisomatic and dendro-axonic areas, suggesting secretion of the protein. At 3 d after KA treatment, strong immunoreactivity is found in astrocytes and in the cell bodies and dendro-axonic projections of resistant neurons such as the dentate granule cells. Taken together, the results suggest that TIMP-1 may be instrumental for neurons and astrocytes in coupling early cellular events triggered by seizures with the regulation of long-lasting changes involved in tissue reorganization and/or neuroprotection.
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PMID:Tissue inhibitor of metalloproteinases-1 (TIMP-1) is differentially induced in neurons and astrocytes after seizures: evidence for developmental, immediate early gene, and lesion response. 915 39

Neuronal cell death in hippocampal remnants was seen after methamphetamine (METH) exposure. Two techniques (Fluoro-Jade labeling and argyrophylia) showed that neuronal degeneration occurred in the indusium griseum, tenia tecta and fasciola cinerea within 5 days post-METH exposure in 70% of the mice. Neurodegeneration also occasionally occurred in the piriform cortex, hippocampus and frontal/parietal cortex. This cell death, unlike striatal neurotoxicity, was not dependent on magnitude of hyperthermia occurring but did correlate with behavioral seizure activity during METH exposure. Excitotoxic mechanisms may be underlying the neuronal degeneration since co-administration of phenobarbital blocked cell death.
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PMID:Methamphetamine exposure can produce neuronal degeneration in mouse hippocampal remnants. 921 71

Neuronal plasticity plays a very important role in brain adaptations to environmental stimuli, disease, and aging processes. The kainic acid model of temporal lobe epilepsy was used to study the long-term anatomical and biochemical changes in the hippocampus after seizures. Using Northern blot analysis, immunocytochemistry, and Western blot analysis, we have found a long-term elevation of the proconvulsive opioid peptide, enkephalin, in the rat hippocampus. We have also demonstrated that an activator protein-1 transcription factor, the 35-kDa fos-related antigen, can be induced and elevated for at least 1 year after kainate treatment. This study demonstrated that a single systemic injection of kainate produces almost permanent increases in the enkephalin and an activator protein-1 transcription factor, the 35-kDa fos-related antigen, in the rat hippocampus, and it is likely that these two events are closely associated with the molecular mechanisms of induction of long-lasting enhanced seizure susceptibility in the kainate-induced seizure model. The long-term expression of the proenkephalin mRNA and its peptides in the kainate-treated rat hippocampus also suggests an important role in the recurrent seizures of temporal lobe epilepsy.
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PMID:A single dose of kainic acid elevates the levels of enkephalins and activator protein-1 transcription factors in the hippocampus for up to 1 year. 925 98

Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-D-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy.
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PMID:Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures. 929 28

Development of audiogenic seizures (AGS) and their correlation with neurodegeneration were studied after 7.5 min of whole-brain ischemia. One day post-ischemia, all animals became hyperreactive and responded to auditory stimulation by generalized seizures. Neuronal necrosis developed already 6 h post-ischemia in inferior colliculi, reticular thalamic nucleus and hippocampal hilar region. Repeated ischemia did not induce any neurological changes, suggesting that the neurological effects are consequences of selective neuronal injury.
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PMID:Audiogenic seizures after neck tourniquet-induced cerebral ischemia in the rat. 935 13

A frequent abnormality in temporal lobes (TL) resected for pharmacoresistant epilepsy is the presence of heterotopic neurons within white matter (WM). We compared heterotopic neuron density in 22 TLs surgically resected from epilepsy patients with TLs from 22 non-neurologic cases obtained at autopsies. Neuronal density was assessed on LFB-PAS-stained and parallel sections immunoreacted for microtubule-associated-protein-2 (MAP-2). The white matter area was outlined by an image analysis system. Neurons, identified by morphologic features, were counted within the marked area. Results are expressed as mean +/- SD neurons/mm2. LFB/PAS sections: Epilepsy cases 4.11 +/- 1.86 Autopsy (normal) 2.35 +/- 0.96; MAP-2 sections: Epilepsy cases 4.08 +/- 1.22, autopsy (normal) 1.68 +/-0.92 (significant at 0.05 level by Wilcoxon's Rank Sums test). The lower number of MAP-2-immunopositive neurons in the control group as compared with the histologically identified group is most likely the result of antigen degradation resulting from an increased postmortem interval. These results indicate that normal TLWM contains a heterotopic population of neurons, and that this neuronal density is significantly higher in epilepsy patients. It is felt that this increased neuronal density is an epiphenomenon rather than the cause of seizures, and may be the result of decreased white matter either secondary to disruption of myelination, or loss of neurons as part of mesial temporal sclerosis.
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PMID:White matter neuronal heterotopia in temporal lobe epilepsy: a morphometric and immunohistochemical study. 941 76

The study explored for the first time the quantitative dentate hilar cell damage in relation to the duration of limbic status epilepticus (SE) induced with electric stimulation on naive rats. SE was induced in adult S-D rats with electric stimulation delivered through a stimulating/recording electrode targeted at the right amygdala. Once SE was established, no further stimulation was given. The rats were treated with diazepam at various times to stop SE, and perfused 18 hours later. Naive and sham operated rats served as controls. Horizontal paraffin sections at the level of the ventral hippocampus were stained with acid fuchsin/cresyl violet. Irreversibly damaged neurons in the right dentate hilus were counted. Neuronal damage was absent with sham operation (n = 4, p > 0.05) and 30-min SE (n = 4, p > 0.05), but it became significant with 1 hour (n = 6, p < 0.05) and longer durations (n = 14, p < 0.05) of SE, compared with the naive controls (n = 10). The severity of SE-induced neuronal damage was not related to the current intensity, induction time, stimulation intensity, or number of class 3-5 seizures. We demonstrate for the first time the relation between seizure duration and the severity of dentate hilar cell damage in limbic SE induced by electric stimulation of naive rats. Further study of this model may elucidate the pathophysiology of SE and improve patient care.
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PMID:Dentate hilar cell damage in electric stimulation-induced limbic status epilepticus. 942 65


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