Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018991 (hemiplegia)
 3,997 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rasmussen's encephalitis (RE) is a progressive, rare childhood disease characterized by severe epilepsy, hemiplegia, dementia, and inflammation of the brain. While one mechanism underlying the pathogenesis of RE has been hypothesized to be mediated by production of excitotoxic GluR3 autoantibodies to the AMPA receptor, other neuropathological etiologies have also been indicated. Whole-cell patch clamp recordings of GABA(A) receptor mediated responses were conducted in neurons acutely isolated from an RE patient, and compared to properties of non-focal human temporal cortical neurons. RE neurons appeared similar anatomically to control cortical neurons. Significant differences in GABAergic responses were evident between RE and control neurons. GABA was significantly more potent in RE than in control cortical neurons (EC50 of 13 microM vs 23 microM, respectively). In addition, the overall efficacy of GABA was significantly decreased in RE neurons, associated with a decrease in postsynaptic GABA current density in RE neurons (5.1 pA/microm2) in comparison to controls (9.2 pA/microm2). Augmentation of GABA responses by the benzodiazepine, clonazepam (CNZ), was significantly reduced in RE in comparison to control neurons (34% vs 99% augmentation at 100 nM). The RE-associated reduced functional efficacy and altered pharmacology of neuronal GABA(A) receptors is consistent with overall disinhibition in RE neurons, and could contribute to the generation of the severe epileptic activity evident in this disorder.
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PMID:Physiological analysis of Rasmussen's encephalitis: patch clamp recordings of altered inhibitory neurotransmitter function in resected frontal cortical tissue. 969 97

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.
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PMID:Glutamate in CNS disorders as a target for drug development: an update. 1561 69