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)

Significant increases in local cerebral blood flow during lithium-pilocarpine (Li-P) induced seizure have been reported. We recently found that both acetone and methyl ethyl ketone (MEK) showed anticonvulsive effects in status epilepticus induced by Li-P in rats. In this study, we examined whether MEK also suppressed the enhancement of local cerebral blood flow induced by Li-P with a simplified autoradiographic method using [(14)C]-para-iodo-N-isopropyl amphetamine ([(14)C]-IMP). Significant increases in local cerebral blood flow in the thalamus, hypothalamus, hippocampus and cerebellum were observed in Li-P induced status epilepticus rats. Pretreatment with MEK (8 mmol/kg) completely suppressed the enhancement of local cerebral blood flow to or below the control level in all regions.
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PMID:Inhibitory effect of methyl ethyl ketone upon the enhancement of cerebral blood flow during status epilepticus induced by lithium-pilocarpine. 1960 78

Enhancement of glucose utilization in the brain has been well known during acute seizure in various kinds of animal model of epilepsy. This enhancement of glucose utilization might be related to neural damage in these animal models. Recently, we found that methyl ethyl ketone (MEK) had both anticonvulsive and neuroprotective effects in lithium-pilocapine (Li-pilo) status epilepticus (SE) rat. In this article, we measured the uptake of [(14)C]2-deoxyglucose ([(14)C]DG) in the Li-pilo SE and Li-pilo SE with MEK rat brain in order to assess whether the glucose utilization was a useful biomarker for the detection of efficacy of anticonvulsive compounds. Significant increase of [(14)C]DG uptake (45 min after the injection) in the cerebral cortex, hippocampus, amygdala and thalamus during acute seizure induced by Li-pilo were observed. On the other hand, the initial uptake of [(14)C]DG (1 min after the injection) in the Li-pilo SE rats was not different from the control rats. Therefore, the enhancement of glucose metabolism during acute seizure was due to the facilitation of the rate of phosphorylation process of [(14)C]DG in the brain. Pretreatment with MEK (8 mmol/kg) completely abolished the enhancement of glucose utilization in the Li-pilo SE rats. The present results indicated that glucose utilization in the brain during acute seizure might be a useful biomarker for the evaluation of efficacy of anticonvulsive compounds.
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PMID:Glucose utilization in the brain during acute seizure is a useful biomarker for the evaluation of anticonvulsants: effect of methyl ethyl ketone in lithium-pilocarpine status epilepticus rats. 1987 51

The anticonvulsant effects of acetone have been reported in various animal models of epilepsy. We recently demonstrated that other ketone bodies, methyl ethyl ketone (MEK) and diethyl ketone (DEK), suppressed status epilepticus that was induced by lithium-pilocarpine in rat. In the present study, the anticonvulsant effects of MEK and DEK were evaluated by using four different types of mouse seizure models, which were induced by pentylenetetrazole, kainic acid, methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM), and electroshock. The effects of clonazepam, a typical anticonvulsant, and acetone were also evaluated and compared with MEK and DEK. In this study, MEK (5 and 10 mmol/kg, i.p.) and DEK (2.5 and 5 mmol/kg, i.p.) produced anticonvulsant activity against all types of seizure models. Furthermore, MEK and DEK showed almost the same potencies against four different seizure models used, while clonazepam showed significant higher ED(50) values against kainic acid-induced and electroshock-induced seizure models as compared with the pentylenetetrazole- or DMCM-induced seizure model. In each study, the highest doses of clonazepam (1 or 3mg/kg) did not show clear anticonvulsant effects against the kainic acid- or electroshock-induced seizures. In conclusion, MEK and DEK showed broad-spectra anticonvulsant effects in both chemically- and electroshock-induced experimental seizure models.
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PMID:Anticonvulsant effects of methyl ethyl ketone and diethyl ketone in several types of mouse seizure models. 2055 23

This study aimed to identify key genes (microRNA and messenger RNA (mRNA)) and associated signaling-regulated pathways in a drug-induced epilepsy model in mice by microarray profiling. The related microarray dataset of seizures was obtained from the NCBI Gene Expression Omnibus database (GEO), and differentially expressed genes (DEGs) between two control samples or multi-treated samples and samples were analyzed using the statistical software R. To identify the expected function of DEGs, Gene Set Enrichment Analysis (GSEA) was utilized to conduct Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The interaction relationship between microRNAs (miRNAs) and mRNAs in normal and epilepsy mouse models was identified using Cytoscape software. TargetScan7.1 was applied to determine the binding sites of DEGs. The dual-luciferase assay was used to verify the target relationship between miRNA and mRNA. Four miRNAs were identified as differentially expressed genes in both 24-h and 28-day status epilepticus (SE)-treated samples. Ppp2ca expression in the mitogen-activated protein kinase (MAPK) signaling pathway was downregulated in the pilocarpine-induced SE mouse model. The expression of Ppp2ca was also downregulated in the kinase-induced SE model group compared with that in the untreated group and MAP kinase (MEK) inhibitor-treated group of mice. KEGG pathway analysis indicated that the MAPK signaling pathway was upregulated in the kinase-induced SE model group compared with that in both the untreated group and the MEK inhibitor-treated group of mice. miR-203 had a targeted relationship with Ppp2ca in both humans and mice. The miR-203-3p target Ppp2ca aggravates the seizures of the SE model in mice.
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PMID:Bioinformatics Analysis of Microarray Profiling Identifies That the miR-203-3p Target Ppp2ca Aggravates Seizure Activity in Mice. 3012 17