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

Pilocarpine-induced status epilepticus (SE) mimics many features of temporal lobe epilepsy and is a useful model to study neural changes that result from prolonged seizure activity. In this study, distribution of the anti-adhesive extracellular matrix protein SC1 was examined in the rat hippocampus following SE. Western blotting showed decreased levels of SC1 protein in the week following SE. Immunohistochemistry demonstrated that the decrease in overall SC1 protein levels was reflected by a reduction of SC1 signal in granule cells of the dentate gyrus. Interestingly, levels of SC1 protein in neurons of the seizure-resistant CA2 sector of the hippocampus did not change throughout the seizure time course. However, at 1 day post-SE, a subset of neurons of the hippocampal CA1, CA3, and hilar regions, which are noted for extensive neuronal degeneration after SE, exhibited a transient increase in SC1 signal. Neurons exhibiting enhanced SC1 signal were not detected at 7 days post-SE. The cellular stress response was also examined. A prominent induction of heat-shock protein (Hsp70) and Hsp27 was detected following SE, while levels of constitutively expressed Hsp40, Hsp90, Hsp110, and Hsc70 showed little change at the time points examined. The subset of neurons that demonstrated a transient increase in SC1 colocalized with the cellular stress marker Hsp70, the degeneration marker Fluoro-Jade B, and the neuron activity marker activity-regulated cytoskeleton-associated protein (Arc). Taken together, these findings suggest that SC1 may be a component of the 'matrix response' involved in remodeling events associated with neuronal degeneration following neural injury.
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PMID:Extracellular matrix protein SC1/hevin in the hippocampus following pilocarpine-induced status epilepticus. 1880 51

During the course of this study, we sought examine whether the expression of somatostatin receptors (SSTRs) is altered in the hippocampus following pilocarpine-induced status epilepticus (SE) in order to understand the role/function of SSTRs in the hippocampus after epileptogenic insults. SSTR1 and SSTR4 immunoreactivities were increased in the hippocampus at 1 week after SE. At 4 weeks after SE, SRIF1-family (SSTR 2A, SSTR2B, and SSTR5) immunoreactivity was increased only in neuropil. Both SSTR2A and 2B immunoreactivities were increased in CA2-3 pyramidal cells. However, SSTR3 and SSTR4 immunoreactivities were reduced in the CA1 pyramidal cells of epileptic rat due to neuronal loss. In addition, SSTR5 immunoreactivity was reduced in CA2 pyramidal cells and various interneurons. Both SSTR2B and SSTR4 immunoreactivities were increased within microglia following SE. Our findings suggest that increases in neuron-glial SSTR expressions may be closely related to the enhanced inhibition of the dentate gyrus and regulation of reactive microgliosis in the hippocampus of a pilocarpine model of temporal lobe epilepsy.
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PMID:The expression of somatostatin receptors in the hippocampus of pilocarpine-induced rat epilepsy model. 1895 27

Temporal lobe epilepsy (TLE) is the most resistant type of epilepsy. Currently available drugs for epilepsy are not antiepileptogenic. A novel treatment for epilepsy would be to block or reverse the process of epileptogenesis. We used intermittent feeding (IF) regimen of the dietary restriction (DR) to study its effect on epileptogenesis and neuroprotection in the pilocarpine model of TLE in rats. The effect of IF regimen on the induction of status epilepticus (SE), the duration of latent period, and the frequency, duration, severity and the time of occurrence of Spontaneous Recurrent Seizures (SRS) were investigated. We also studied the effect of IF regimen on hippocampal neurons against the excitotoxic damage of prolonged SE (about 4h) induced by pilocarpine. The animals (Wistar, male, 200-250g) were divided into four main groups: AL-AL (ad libitum diet throughout), AL-IF (PfS) [IF post-first seizure], AL-IF (PSE) [IF post-SE] and IF-IF (IF diet throughout), and two AL and IF control groups. SE was induced by pilocarpine (350mg/kg, i.p.) and with diazepam (6mg/kg, i.p.) injected after 3h, the behavioral signs of SE terminated at about 4h (AL animals, n=29, 260.43+/-8.74min; IF animals, n=19, 224.32+/-20.73min). Behavioral monitoring was carried out by 24h video recording for 3 weeks after the first SRS. Rat brains were then prepared for histological study with Nissl stain and cell counting was done in CA1, CA2 and CA3 regions of the hippocampus. The results show that the animals on IF diet had significantly less SE induction and significantly longer duration of latent period (the period of epileptogenesis) was seen in IF-IF group compared to the AL-AL group. The severity of SRS was significantly more in AL-IF (PfS) compared to the AL-IF (PSE) group. These results indicate that IF diet can make rats resistant to the induction of SE and can prolong the process of epileptogenesis. The results of the histological study show that the number of pyramidal neurons was statistically less in CA1, CA2 and CA3 of the hippocampus in the experimental groups compared to the control groups. However, IF regimen could not protect the hippocampal neurons against the excitotoxic injury caused by a prolonged SE. We conclude that IF regimen can significantly influence various behavioral characteristics of pilocarpine model of TLE. Further studies can elaborate the exact mechanisms as well as its possible role in the treatment of human TLE.
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PMID:Behavioral and histological assessment of the effect of intermittent feeding in the pilocarpine model of temporal lobe epilepsy. 1950 98

Status epilepticus triggers a mixture of apoptotic and necrotic cell death within the hippocampus. This neuronal loss may result in the development of epilepsy and cognitive deficits. Erythropoietin mediates a number of biological actions within the central nervous system and has been shown to be neuroprotective. In the present study, we investigated the effects of recombinant human erythropoietin on hippocampus of rat after lithium-pilocarpine induced status epilepticus. Twenty-one dam reared Wistar male rats, 21-day-old were divided into three groups: control group, lithium-pilocarpine induced status epilepticus and lithium-pilocarpine induced status epilepticus and erythropoietin treated group. Erythropoietin treated group received recombinant human erythropoietin 10 U/g intraperitoneally 40 min after pilocarpine injection for 5 days. Rats were sacrificed and brain tissues were collected at 5th day of experiment. Neuronal cell death and apoptosis were evaluated. Histopathological examination showed that erythropoietin significantly decreased neuronal cell death in CA1, CA2, CA3 and dentate gyrus regions of hippocampus. It also diminished apoptosis in the CA1 and dentate gyrus regions of hippocampus. In conclusion, erythropoietin may preserve the number of neurons and decrease apoptosis in model of status epilepticus induced by lithium-pilocarpine. This experimental study suggests that erythropoietin administration may be neuroprotective in status epilepticus.
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PMID:Neuroprotective effects of recombinant human erythropoietin in the developing brain of rat after lithium-pilocarpine induced status epilepticus. 2160 Jul 13

California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy.
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PMID:Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions (Zalophus californianus). 2463 60

P450 metabolic enzymes are expressed in the human and rodent brain. Recent data support their involvement in the pathophysiology of epilepsy. However, the determinants of metabolic enzyme expression in the epileptic brain are unclear. We tested the hypothesis that status epilepticus (SE) or exposure to phenytoin or phenobarbital affects brain expression of the metabolic enzyme CYP2E1. SE was induced in C57BL/6J mice by systemic kainic acid. Brain CYP2E1 expression was evaluated 18-24h after severe SE by immunohistochemistry. Co-localization with neuronal nuclei (NEUN), glial fibrillary acidic protein (GFAP) and CD31 was determined by confocal microscopy. The effect of phenytoin, carbamazepine and phenobarbital on CYP2E1 expression was evaluated in vivo or by using organotypic hippocampal cultures in vitro. CYP2E1 expression was investigated in brain resections from a cohort of drug-resistant epileptic brain resections and human endothelial cultures (EPI-EC). Immunohistochemistry showed an increase of CYP2E1 expression limited to hippocampal CA2/3 and hilar neurons after severe SE in mice. CYP2E1 expression was also observed at the astrocyte-vascular interface. Analysis of human brain specimens revealed CYP2E1 expression in neurons and vascular endothelial cells (EC). CYP2E1 was expressed in cultured human EC and over-expressed by EPI-EC. When analyzing the effect of drug exposure on CYP2E1 expression we found that, in vivo or in vitro, ethanol increased CYP2E1 levels in the brain and liver. Treatment with phenytoin induced localized CYP2E1 expression in the brain whereas no significant effects were exerted by carbamazepine or phenobarbital. Our data indicate that the effect of acute SE on brain CYP2E1 expression is localized and cell specific. Exposure to selected anti-epileptic drugs could play a role in determining CYP2E1 brain expression. Additional investigation is required to fully reproduce the culprits of P450 enzyme expression as observed in the human epileptic brain.
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PMID:Effect of status epilepticus and antiepileptic drugs on CYP2E1 brain expression. 2528 Jul 86

Hippocalcin participates in the maintenance of neuronal calcium homeostasis. In the present study, we examined the time-course changes of neuronal degeneration and hippocalcin protein level in the mouse hippocampus following pilocarpine-induced status epilepticus (SE). Marked neuronal degeneration was observed in the hippocampus after SE in a time-dependent manner, although neuronal degeneration differed according to the hippocampal subregions. Almost no hippocalcin immunoreactivity was detected in the pyramidal neurons of the cornu ammonis 1 (CA1) region from 6 h after SE. However, many pyramidal neurons in the CA2 region showed hippocalcin immunoreactivity until 24 h after SE. In the CA3 region, only a few hippocalcin immunoreactive cells were observed at 12 h after SE, and almost no hippocalcin immunoreactivity was observed in the pyramidal neurons from 24 h after SE. Hippocalcin immunoreactivity in the polymorphic cells of the dentate gyrus was markedly decreased from 6 h after SE. In addition, hippocalcin protein level in the hippocampus began to decrease from 6 h after SE, and was significantly decreased at 24 h and 48 h after pilocarpine-induced SE. These results indicate that marked reduction of hippocalcin level may be closely related to neuronal degeneration in the hippocampus following pilocarpine-induced SE.
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PMID:Time-course changes of hippocalcin expression in the mouse hippocampus following pilocarpine-induced status epilepticus. 2643 44

Dentate granule cell (DGC) mossy fiber sprouting (MFS) in mesial temporal lobe epilepsy (mTLE) is thought to underlie the creation of aberrant circuitry which promotes the generation or spread of spontaneous seizure activity. Understanding the extent to which populations of DGCs participate in this circuitry could help determine how it develops and potentially identify therapeutic targets for regulating aberrant network activity. In this study, we investigated how DGC birthdate influences participation in MFS and other aspects of axonal plasticity using the rat pilocarpine-induced status epilepticus (SE) model of mTLE. We injected a retrovirus (RV) carrying a synaptophysin-yellow fluorescent protein (syp-YFP) fusion construct to birthdate DGCs and brightly label their axon terminals, and compared DGCs born during the neonatal period with those generated in adulthood. We found that both neonatal and adult-born DGC populations participate, to a similar extent, in SE-induced MFS within the dentate gyrus inner molecular layer (IML). SE did not alter hilar MF bouton density compared to sham-treated controls, but adult-born DGC bouton density was greater in the IML than in the hilus after SE. Interestingly, we also observed MF axonal reorganization in area CA2 in epileptic rats, and these changes arose from DGCs generated both neonatally and in adulthood. These data indicate that both neonatal and adult-generated DGCs contribute to axonal reorganization in the rat pilocarpine mTLE model, and indicate a more complex relationship between DGC age and participation in seizure-related plasticity than was previously thought.
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PMID:Axonal plasticity of age-defined dentate granule cells in a rat model of mesial temporal lobe epilepsy. 2664 85

Recent studies about the novel antidepressant agomelatine, which is a mixed MT1 and MT2 melatonin receptor agonist and 5HT2C serotonin receptor antagonist possessing an anticonvulsant and neuroprotective action, suggest that it may have potential to contribute against epileptogenesis and epilepsy-induced memory impairment. In order to ascertain whether protection of some brain structures could suppress epileptogenesis, in the present study, we evaluated the effect of chronic post-status treatment with agomelatine on epileptogenesis, behavioral and neuronal damage induced by kainate acid (KA) status epilepticus (SE). Agomelatine/vehicle treatment (40mg/kg, i.p.) started one hour after SE and continued up to 10weeks in Wistar rats. Latency for onset of spontaneous motor seizures (SMS) and their frequency was detected by a 24-h video-recording. Locomotor activity, anxiety and hippocampus-dependent spatial memory in open field (OF), elevated plus maze (EPM), light-dark test (LDT) and radial arm maze (RAM) test, respectively, were evaluated during the last two weeks after SE. Agomelatine significantly decreased the latency for onset of SMS and increased the seizure frequency during the 2nd and the 3rd week of treatment. The MT1 and MT2 receptor agonist and serotonin 5HT2C receptor antagonist exacerbated the KA-induced hyperlocomotion and impulsive behavior and it was unable to prevent spatial memory impairment of epileptic rats. However, agomelatine induced a neuroprotection in the dorsal hippocampus, specifically in the CA1, septal CA2 and partially in the CA3c region, the hilus of the dentate gyrus, piriform cortex and septo-temporal and temporal basolateral amygdala. Our findings suggest that the beneficial impact against SE-induced neuronal loss exerted by agomelatine is not crucial for the suppression of epileptogenesis and its deleterious consequences in KA model of temporal lobe epilepsy.
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PMID:Agomelatine protects against neuronal damage without preventing epileptogenesis in the kainate model of temporal lobe epilepsy. 2843 4

Soman (GD) exposure results in status epilepticus (SE) that leads to neurodegeneration, neuroinflammation, and behavioral consequences including learning and memory deficits. The neuroinflammatory response is characterized by the upregulation of the pro-inflammatory cytokine, interleukin-1 (IL-1), which mediates the expression of other neurotoxic cytokines induced after GD exposure. However, the specific role of IL-1 signaling has not been defined in terms of the consequences of GD-induced SE. Therefore, the purpose of this study was to regulate IL-1 signaling and study the behavioral deficits and neurodegeneration that occur after convulsion onset. Wild type (WT), IL-1 receptor (IL-1R1) knockout (KO), and IL-1 receptor antagonist (IL-1Ra) KO mice were exposed to a convulsive dose of GD, and behavior was evaluated up to 18days later. Activity was studied using the Open Field, anxiety was assessed in the Zero Maze, and spatial learning and memory were evaluated with the Barnes Maze. The animals were euthanized at 24hours and 18days to determine neuropathology in the piriform cortex, amygdala, thalamus, and CA1, CA2/3, and CA4 regions of the hippocampus. Unlike the IL-1Ra KO, the IL-1R1 KO showed less neuropathology compared to WT at 24hours, but moderate to severe injury was found in all strains at 18days. Compared to their saline controls, the exposed WT mice were significantly more active in the Open Field, and the IL-1R1 KO strain showed reduced anxiety in the Zero Maze Test. Compared to WT mice, IL-1R1 and IL-1Ra KO mice had spatial learning and memory impairments in the Barnes Maze. Therefore, the IL-1 signaling pathway affects neurodegeneration and behavior after GD-induced convulsions.
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PMID:Neuropathological and behavioral sequelae in IL-1R1 and IL-1Ra gene knockout mice after soman (GD) exposure. 2886 71


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