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)

Studies of neuroactive amino acids and their regulatory enzymes in surgically excised focally epileptic human brain are reviewed. Concentrations of glutamate, aspartate and glycine are significantly increased in epileptogenic cerebral cortex. The activities of the enzymes, glutamate dehydrogenase and aspartate aminotransferase, involved in glutamate and aspartate metabolism are also increased. Polyamine synthesis is enhanced in epileptogenic cortex and may contribute to the activation of N-methyl-D-aspartate (NMDA) receptors. Nuclear magnetic resonance spectroscopy (NMRS) reveals that patients with poorly controlled complex partial seizures have a significant diminution in occipital lobe gamma aminobutyric acid (GABA) concentration. The activity of the enzyme GABA-aminotransaminase (GABA-T) which catalyzes GABA degradation is not altered in epileptogenic cortex. NMRS studies show that vigabatrin, a GABA-T inhibitor and effective antiepileptic, significantly increases brain GABA. Glutamate decarboxylase (GAD), responsible for GABA synthesis, is diminished in interneurons in discrete regions of epileptogenic cortex and hippocampus. In vivo microdialysis performed in epilepsy surgery patients provides measurements of extracellular amino acid levels during spontaneous seizures. Glutamate concentrations are higher in epileptic hippocampi and increase before seizure onset reaching potentially excitotoxic levels. Frontal or temporal cortical epileptogenic foci also release aspartate, glutamate and serine particularly during intense seizures or status epilepticus. GABA in contrast, exhibits a delayed and feeble rise in the epileptic hippocampus possibly due to a reduction in the number and/or efficiency of GABA transporters.
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PMID:Neuroactive amino acids in focally epileptic human brain: a review. 1055 79

The aim of the study was to investigate the changes in biochemical mechanisms facilitating cellular damages in the lithium plus pilocarpine treatment and the resulting status epilepticus. The whole brain free fatty acid (FFA) level as well as the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), glutamate dehydrogenase, aspartate-aminotransferase (AST), alanine-aminotransferase, gamma-glutamoyl transferase, alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and creatine kinase in the frontal cortex, cerebellum, hippocampus and pons-medulla region of Hannover-Wistar rats were determined. The control group was intact with no previous experimental history. LiCl (125 mg/kg i.p.) was injected 20 h prior to pilocarpine (30 mg/kg i.p.) and the treated rats were sacrificed 1 or 2 1/2 h after pilocarpine administration. The results show that lithium plus pilocarpine administration and the resulting status epilepticus produced the significant increase of the brain FFA content. Decreased GPX activities were detected in the frontal cortex, cerebellum and hippocampus of the treated rats without the accompanying decrease of SOD activity. Increased AST and LDH activities were observed in the frontal cortex, increased soluble ALP activities in the frontal cortex and pons-medulla region whereas the increased activity of membrane bound ALP was detected in the hippocampus of the rats with status epilepticus. Activities of the other analysed enzymes did not change in the examined brain regions. The presented data indicate clear regional differences of biochemical changes caused by lithium plus pilocarpine treatment and the resulting status epilepticus, frontal cortex being the most affected site.
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PMID:Lithium plus pilocarpine induced status epilepticus--biochemical changes. 1071 13

Recent studies have demonstrated that blockade of neuronal death in the hippocampus cannot prevent epileptogenesis in various epileptic models. These reports indicate that neurodegeneration alone is insufficient to cause epilepsy, and that the role of astrocytes in epileptogenesis should be reconsidered. Therefore, the present study was designed to elucidate whether altered morphological organization or the functionalities of astrocytes induced by status epilepticus (SE) is responsible for epileptogenesis. Glial responses (reactive microgliosis followed by astroglial death) in the dentate gyrus induced by pilocarpine-induced SE were found to precede neuronal damage and these alterations were closely related to abnormal neurotransmission related to altered vesicular glutamate and GABA transporter expressions, and mossy fiber sprouting in the dentate gyrus. In addition, newly generated astrocytes showed down-regulated expressions of glutamine synthase, glutamate dehydrogenase, and glial GABA transporter. Taken together, our findings suggest that glial responses after SE may contribute to epileptogenesis and the acquisition of the properties of the epileptic hippocampus. Thus, we believe that it is worth considering new therapeutic approaches to epileptogenesis involving targeting the inactivation of microglia and protecting against astroglial loss.
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PMID:Epileptogenic roles of astroglial death and regeneration in the dentate gyrus of experimental temporal lobe epilepsy. 1684 74