Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both the amygdala and hippocampus are damaged in drug-resistant temporal lobe epilepsy (TLE), suggesting that amygdalo-hippocampal interconnectivity is compromised in TLE. Therefore, we examined one of the major projections from the amygdala to the hippocampus, the projection from the amygdala to the CA1 subfield of the hippocampus/subiculum border region, and assessed whether it is preserved in rats with spontaneous seizures. Male Wistar rats were injected with kainic acid (9 mg/kg, i.p.) to induce chronic epilepsy. The occurrence of spontaneous seizures was monitored 5 or 15 weeks later by video-recording the rats for up to 5 days. Saline-injected animals served as controls. Thereafter, the retrograde tracer Fluoro-gold was injected into the border region of the temporal CA1/subiculum. Rats were perfused for histology 1-2 weeks later and sections were immunohistochemically processed to detect Fluoro-gold-positive cells. Comparison of the labeling in control and epileptic tissue indicated that a large cluster of retrogradely labeled cells in the parvicellular division of the basal nucleus was well preserved in epilepsy, even when the neuronal damage in the amygdala was substantial. Another large cluster of retrogradely labeled cells in the lateral division of the amygdalo-hippocampal area, the posterior cortical nucleus (part of the vomeronasal amygdala), and the periamygdaloid cortex (part of the olfactory amygdala), however, had disappeared in epileptic brain in parallel to severe neuronal loss in these nuclei. These data demonstrate that a projection from the parvicellular division of the basal nucleus to the temporal CA1/subiculum region is resistant to status epilepticus-induced neuronal damage and provides a candidate pathway by which seizure activity can spread and propagate from the amygdala to the hippocampal formation.
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PMID:Damage to the amygdalo-hippocampal projection in temporal lobe epilepsy: a tract-tracing study in chronic epileptic rats. 1520 66

The present study examined the effects of a free radical scavenger, N-tert-butyl-alfa-phenylnitrone (PBN) on lithium-pilocarpine-induced status epilepticus (SE) and its short-term consequences in rats 12 (P12) or 25 (P25) days old. PBN (2 x 100 mg/kg i.p.) was injected according to the following schedules: 1) PBN-pretreated animals received the first dose 30 min prior to pilocarpine, the second dose was given 1 min after SE onset, and 2) PBN-treated animals received the first dose of PBN 1 min after SE onset and the second one 60 min later. Paraldehyde was administered to decrease mortality. Effects of PBN were highly age-dependent. In P25 group, PBN-pretreatment increased latency to SE onset and significantly suppressed the severity of motor manifestation of SE. Both PBN pretreatment and treatment improved recovery after SE. In contrast, administration of PBN in P12 animals did not affect SE pattern or recovery after SE. Administration of PBN had no effects on the motor performance of animals 3 and 6 days after SE. Neuronal damage was examined 24 h and 7 days after SE using Fluoro-Jade B staining. Mild neuroprotective effects of PBN in hippocampal fields CA1 and CA3 occurred in P25 rats in both experimental schedules. In contrast, administration of PBN aggravated neuronal injury in the hippocampus in P12 rats. Administration of PBN to intact rats did not induce neurodegeneration in either age group.
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PMID:Effects of a free radical scavenger N-tert-butyl-alpha-phenylnitrone (PBN) on short-term recovery of immature rats after status epilepticus. 1554 25

To better understand the role of inflammatory responses in temporal lobe epilepsy, we characterized Interleukin1-beta (IL1-beta), Nuclear Factor-kappaB (NF-kappaB), and Cyclooxygenase-2 (COX-2) expression together with neurodegeneration in the rat lithium-pilocarpine model. The immunohistochemical expression of IL1-beta, NF-kappaB, and COX-2 started by 12 h post-injection, persisted for 24 h (status epilepticus period), and returned to basal levels by 3 and 6 days (latent period). The regional distribution of IL1-beta, NF-kappaB, and COX-2 occurred mainly in structures prone to develop neuronal damage. Using double-staining protocols, we detected IL1-beta expression in glial cells, COX-2 expression in neurons, and NF-kappaB in both cell types. The presence of Fluoro-Jade-B-positive degenerating neurons was associated with IL1-beta, NF-kappaB, and COX-2 proteins expression during status epilepticus but not during the latent period while neurons were still degenerating. These data suggest that seizure-related IL1-beta, NF-kappaB, and COX-2 expression may contribute to the pathophysiology of epilepsy by inducing neuronal death and astrocytic activation.
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PMID:Temporal patterns of the cerebral inflammatory response in the rat lithium-pilocarpine model of temporal lobe epilepsy. 1557 75

Many animal models have been established to study the mechanisms leading to excitotoxicity. One of the more commonly used models is kainic acid (KA) induced excitotoxicity. Upon administration of KA in rodents, KA produces acute status epilepticus and neuronal damage. The aim of the study was to examine the morphologic alteration in the hippocampus of mature rats, after repeated KA administration. The first group was given KA repeatedly in six doses (10 mg/1000 g), each second day. The second group was given KA i.p. repeatedly in six smaller doses (5 mg/1000 g), each second day. The third group (control animals) received corresponding volumes of the normal saline (5 or 10 mg/1000 g respectively). Animals were transcardially perfused; serial sections were stained with Fluoro-Jade B and DNA-specific dye bis-benzimide (Hoechst). In CA1 region of the first group many degenerating cells were observed. The CA2 region was not as much affected as CA1. In the CA3 region no degenerating cells were observed. In the second group the most prominent was the cell loss both in the CA3 region and in the hilus of the dentate gyrus.
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PMID:Repeated kainic acid administration and hippocampal neuronal degeneration. 1600 12

Stroke is a major cause of epilepsy, but the molecular mechanisms underlying post-stroke epileptogenesis are unknown. The expression of cystatin C, a cysteine protease inhibitor, is increased in the hippocampus during status epilepticus (SE)-induced epileptogenesis, and regulates both cell death and birth. To test the hypothesis that increased cystatin C expression represents a common molecular alteration induced by epileptogenic brain insults, we investigated the time course, cellular localization, and association of cystatin C expression with neuronal damage during post-stroke epileptogenesis. Stroke was induced with photothrombosis, which leads to epilepsy in approximately 20-30% of rats. Cystatin C expression was increased in the CA1 area of the hippocampus 4 days after photothrombosis, when the diameter of the lesion was the largest. Double-labeling and confocal analysis indicated that cystatin C was expressed in astrocytes and microglia. Unlike after SE, cystatin C expression did not change in the dentate gyrus. Also, increased cystatin C expression was not associated with neurodegeneration, which was demonstrated as an absence of Fluoro Jade B-positive cells in adjacent sections. The present study provides evidence that cystatin C may be involved in cellular alterations that occur after an epileptogenic insult, not only after SE but also after photothrombotic stroke.
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PMID:Cystatin C expression is increased in the hippocampus following photothrombotic stroke in rat. 1630 30

Glutamate excitotoxicity has been involved in the pathophysiology of epilepsy. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. Using densitometric immunohistochemical analysis, we examined the temporal expression of the neuronal glutamate transporter (EAAC1) in the lithium-pilocarpine rat model of temporal lobe epilepsy. During the acute period of lithium-pilocarpine-induced status epilepticus, EAAC1 transporter expression increased in the pyramidal neurons of cornus ammonis (CA)1, CA2 and CA3 (fields of the hippocampus), in dentate gyrus (DG) granule cells and in olfactory tubercle (Tu). During the latent period, EAAC1 expression was strongly expressed in the DG granular and molecular layers, Tu, cerebral cortex and septum, and went back to control levels in CA1, CA2 and CA3 layers. The overexpression of EAAC1 occurred mainly in structures prone to develop Fluoro-Jade-B-positive degenerating neurons. It is, however, not clear to what extent the overexpression of EAAC1 contributes to epileptogenesis and in which area it may represent a preventive or compensatory or response to injury.
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PMID:EAAC1 glutamate transporter expression in the rat lithium-pilocarpine model of temporal lobe epilepsy. 1653 32

Histological examination of brain after a single high (40 mg/kg) dose of D-methamphetamine (METH) was used to determine the relationships between blood-brain barrier (BBB) disruption, hyperthermia, intense seizure activity, and extensive degeneration that this exposure often produces. In very hyperthermic mice (body temperatures > 40.5 degrees C) exhibiting status epilepticus, increase in mouse IgG immunoreactivity (IgGIR) in the medial and ventral amygdala was observed within 90 min after METH exposure. In a few instances, where body temperature was in the 40.0 degrees C range, such IgGIR was also seen in animals that had exhibited status epilepticus. Variable increases in IgGIR, which correlated with neurodegeneration, also occurred within 12 h in the hippocampus, indicating BBB disruption in this region also. Degenerating neurons, Fluoro-Jade C (FJ-C) labeled, were first detected 4 h after METH in the amygdala and hippocampus. Extensive neurodegeneration occurred in the amygdaloid and hippocampal pyramidal cell regions in animals with marked IgGIR increase in these regions by 12 and 24 h after METH. A very rapid activation of brain microglia and/or infiltration of macrophages in regions of notable IgGIR increase with intense neurodegeneration were seen within 24 h. The phagocytosis rate of neurons in the hippocampus was so rapid that FJ-C labeling was virtually nonexistent 3 days after METH. METH did not produce IgGIR increase or neurodegeneration in the limbic regions in the absence of hyperthermia and seizures. Thus, high doses of METH can cause damage to the BBB when hyperthermia occurs, resulting in rapid and extensive hippocampal and amygdalar damage. The BBB disruption in the medial amygdala occurs first, and may well be contributing to the induction and severity of seizures, while BBB disruption in the hippocampus is likely a result of the seizures and hyperthermia. This hippocampal damage should be sufficient to compromise learning and memory.
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PMID:High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus. 1695 62

Neuropeptide-containing hippocampal interneurons and dentate granule cell inhibition were investigated at different periods following electrical stimulation-induced, self-sustaining status epilepticus (SE) in rats. Immunohistochemistry for somatostatin (SOM), neuropeptide Y (NPY), parvalbumin (PV), cholecystokinin (CCK), and Fluoro-Jade B was performed on sections from hippocampus contralateral to the stimulated side and studied by confocal laser scanning microscopy. Compared to paired age-matched control animals, there were fewer SOM and NPY-immunoreactive (IR) interneurons in the hilus of the dentate gyrus in animals with epilepsy (40-60 days after SE), and 1, 3, and 7 days following SE. In the hilus of animals that had recently undergone SE, some SOM-IR and NPY-IR interneurons also stained for Fluoro-Jade B. Furthermore, there was electron microscopic evidence of the degeneration of SOM-IR interneurons following SE. In contrast, the number of CCK and PV-IR basket cells in epileptic animals was similar to that in controls, although it was transiently diminished following SE; there was no evidence of degeneration of CCK or PV-IR interneurons. Patch-clamp recordings revealed a diminished frequency of inhibitory postsynaptic currents in dentate granule cells (DGCs) recorded from epileptic animals and animals that had recently undergone SE compared with controls. These results confirm the selective vulnerability of a particular subset of dentate hilar interneurons after prolonged SE. This loss may contribute to the reduced GABAergic synaptic inhibition of granule cells in epileptic animals.
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PMID:Selective loss of dentate hilar interneurons contributes to reduced synaptic inhibition of granule cells in an electrical stimulation-based animal model of temporal lobe epilepsy. 1717 60

Neurogenesis in the suprapyramidal and infrapyramidal blades of the rostral dentate gyrus was investigated following kainic acid (KA)-induced status epilepticus (SE) in adult rats. Rats were injected with KA (14 mg/kg, i.p.) or saline, with convulsions terminated by an intraperitoneal injection of diazepam. Five days after the induction of SE, the rats were injected with 5-bromo-2-deoxyuridine-5-monophosphate (BrdU; 75 mg/kg, i.p.), a marker of cell division. One day after the BrdU injection, the numbers of BrdU-labeled cells in the supra- and infrapyramidal blades were significantly higher in the KA-injected rats compared to the saline-injected rats. In the saline-injected rats, the number of BrdU-labeled cells in the infrapyramidal blade was greater than in the suprapyramidal blade. Twenty-eight days after the BrdU injection, the number of BrdU-labeled cells remained significantly higher in the KA-injected rats than the saline-injected rats, but only in the infrapyramidal blade. In addition, when the extent of cell death was examined with Fluoro-Jade B (a marker of dead and dying cells) 3 days after the induction of SE, degenerating cells were more numerous in the infrapyramidal blade than in the suprapyramidal blade. Our results suggest that there is an asymmetry of neurogenesis and cell death in the rostral dentate gyrus of rats following KA-induced SE.
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PMID:Asymmetry in enhanced neurogenesis in the rostral dentate gyrus following kainic acid-induced status epilepticus in adult rats. 1761 86

Status epilepticus may cause long-term functional and structural consequences possibly resulting in brain dysfunctions such as chronic epilepsy. In epileptogenesis, the dentate gyrus plays a key role in regulating the excitability of highly vulnerable and potentially epileptogenic downstream structures in the hippocampus proper. One, four and eight weeks after electrically induced status epilepticus, excitability and neuronal degeneration in the rat dentate gyrus were examined with intracerebral electrodes and Fluoro Jade (FJ) staining, respectively. Half of the animals had developed chronic epilepsy by 8 weeks after status epilepticus. Sham-operated controls did not exhibit seizures, and the excitatory parameters remained unchanged. Compared to controls, 8 weeks after status epilepticus the population spike latency in the dentate gyrus was significantly reduced (p<0.05) and substantial neuronal degeneration was seen (p<0.05). In summary, status epilepticus results in functional and morphological alterations in the dentate gyrus likely contributing to epileptogenesis.
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PMID:Functional and morphological changes in the dentate gyrus after experimental status epilepticus. 1772 57


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