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)

A 36-year-old woman presented with partial complex status epilepticus. Magnetic resonance imaging with T2-weighted sequences showed a high-intensity signal in the left posterior frontal area. Hashimoto's thyroiditis was then discovered. The disappearance of the high-intensity signal after corticosteroid therapy was suggestive of an autoimmune mechanism. However, improvement could be obtained only with a hormonal treatment, which supports the hypothesis of a pathogenetic role of the Tyrosine-Releasing Hormone (TRH).
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PMID:[Hashimoto's encephalopathy: toxic or autoimmune mechanism?]. 144 53

Phosphorylation of protein tyrosines is an important modulatory process for cell signaling and other cellular functions. Rat brain regions were examined for altered protein phosphotyrosines, using Western blot analysis and microwave irradiation to limit postmortem alterations, after administration of two convulsants: lithium plus pilocarpine or kainic acid (KA). Most phosphotyrosine proteins were unaltered by these treatments, but there was a large, specific increase in the tyrosine phosphorylation of a 40-Kd protein. This increase was evident in all three regions examined: cerebral cortex, hippocampus, and striatum; it occurred abruptly with onset of generalized status epilepticus (SE) and remained elevated for at least 90 min. Most of the tyrosine phosphorylated 40-Kd protein was in the cytosolic fraction. These results demonstrate a large, specific effect of chemically induced seizures on a single phosphotyrosine protein in rat brain.
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PMID:Seizure-induced protein tyrosine phosphorylation in rat brain regions. 172 Jul 36

We measured the effects of four weeks of dietary lithium treatment and of status epilepticus induced by administration of pilocarpine to lithium-treated rats on the concentrations of amino acids in four regions of rat brain: cerebral cortex, hippocampus, striatum, and substantia nigra. To ensure accurate quantitation of the amino acids, animals were sacrificed by focussed beam microwave irradiation and amino acids were measured using a fully validated triple-column ion-exchanged amino acid analyzer with post-column o-phthalaldehyde derivatization and fluorometric detection. The concentrations of four amino acids, threonine, methionine, lysine and tyrosine, were increased significantly in two to four brain regions by chronic lithium treatment. Their concentrations remained elevated, or were further increased, during status epilepticus. The concentrations of eight amino acids and ammonia were not altered by lithium treatment but increased in concentration during status epilepticus in some brain regions. Glycine, serine, arginine and citrulline were decreased by chronic lithium treatment. Status epilepticus increased the concentrations of these four amino acids above that found in the lithium-treated samples in some of the brain regions that were examined. Six amino acids and glutathione were generally unaltered by both treatments. These results are related to the effects of lithium treatment and are compared with changes reported by others following treatment with a variety of convulsive stimuli.
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PMID:Chronic lithium treatment and status epilepticus induced by lithium and pilocarpine cause selective changes of amino acid concentrations in rat brain regions. 259 48

The incorporation of L-[3,5-3H]tyrosine into cerebral proteins was investigated during the initial phase (30 min) of bicuculline-induced status epilepticus. Autoradiographs of different parts of the cerebral hemispheres, brain stem, and cerebellum were prepared. Marked local reduction of amino acid incorporation was evident in bilaterally symmetrical areas of the cerebral cortex, hippocampus, thalamic nuclei, and the region of the medial geniculate body. No apparent difference of local [3H]tyrosine incorporation was observed in the lower brain stem nuclei and in the cerebellum of control and convulsed animals. The territories showing a decrease of protein synthesis during epileptic seizures coincide largely with the regions of maximal local glucose metabolism and cerebral blood flow. The present investigation demonstrates that autoradiography of regional protein biosynthesis is a suitable method for the visualization of neuronal populations at risk in the very early stages of seizure activity.
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PMID:Regional protein synthesis in the rat brain during bicuculline-induced epileptic seizures. 731 2

Phosphorylation of tyrosine residue in proteins is an important modulatory process for membrane transduction and cell signaling and for several cellular functions. The concentration and distribution of phosphotyrosine proteins were analyzed in the hippocampi of rats in the model of epilepsy induced by pilocarpine using Western blotting and immunohistochemistry. The concentration of several phosphotyrosine proteins increased during status epilepticus. During the seizure-free period and the chronic period of this epilepsy model, the hippocampi of rats did not exhibit changes in the expression of these proteins. Immunohistochemistry showed an increased immunoreactivity throughout the hippocampal formation of rats 1 h after status epilepticus that was acutely induced by pilocarpine. Animals killed after 3 h of status epilepticus showed an increased expression of phosphotyrosine in the hippocampal hilus and CA3 regions. After 5 h of status epilepticus, phosphotyrosine immunoreactivity persisted only in the CA3 region. After 12 h of status epilepticus, the hippocampal formation exhibited a normal phosphotyrosine immunostaining, showing that the increased expression of these proteins is related to the acute phase and that several intracellular events could undergo modifications during the status epilepticus induced by pilocarpine.
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PMID:Tyrosine phosphorylation is increased in the rat hippocampus during the status epilepticus induced by pilocarpine. 976 94

The nonreceptor tyrosine kinase PYK2 represents a stress-sensitive mediator of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase (MAPK) signaling pathways in many cell types. In the present study, we assessed the tyrosine phosphorylation of PYK2 under normal and pathological conditions in the CNS. We generated a polyclonal antibody that selectively recognizes tyrosine-phosphorylated PYK2 at its major autophosphorylation site. By using this antibody, we demonstrate that the phosphorylation profile of PYK2 after focal cerebral ischemia is biphasic. The first phase occurs within 1 hr, when most of the phospho-PYK2 immunoreactivity was observed in cortical neurons, whereas 24-72 hr after ischemia, a striking induction of phospho-PYK2 immunoreactivity was evident in microglia around the necrotic infarcted area. Double-immunostaining analysis using both anti-phospho-PYK2 antibody and antibody against the double-phosphorylated active form of p38MAPK revealed that the two phosphorylated protein kinases exhibit strikingly similar distribution patterns after ischemia. A short time after ischemia, phosphorylation of p38MAPK was evident in the cortical neurons as demonstrated by both immunohistochemistry and immunoblotting analysis, whereas 24-72 hr after ischemia, phospho-p38MAPK was found in activated microglia and colocalized with phospho-PYK2. In contrast to cortical neurons, basal phospho-PYK2 immunoreactivity was observed in hippocampal pyramidal neurons, which was markedly decreased after kainate acid-induced status epilepticus. However, 24 hr after the epileptic onset, a pronounced upregulation of PYK2 and phospho-PYK2 immunoreactivities was evident in microglial cells, as demonstrated by double-immunostaining with the microglial marker OX42. These results provide, for the first time, in situ localization of tyrosine-phosphorylated PYK2 in neuronal stress pathways in the adult rat brain and are consistent with the role of PYK2 as an upstream regulator of p38MAPK signaling cascades in response to stress signals.
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PMID:Cerebral ischemia and seizures induce tyrosine phosphorylation of PYK2 in neurons and microglial cells. 1096 54

Systemic administration of kainic acid (KA) induces status epilepticus (SE) that causes neurodegeneration and may subsequently lead to spontaneous recurrent seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the hippocampus and frontal cortex relative to controls. Tyrosine phosphorylation of the NMDA receptor subunits NR2A and NR2B was also enhanced following SE. Animals that received KA but did not develop SE, did not exhibit increased tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA receptor, and indicate that the interaction of the NMDA receptor with other components of the NMDA receptor complex are altered as a consequence of seizure activity.
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PMID:Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus. 1168 75

Systemic administration of pilocarpine preceded by lithium induces status epilepticus (SE) that results in neurodegeneration and may lead to the development of spontaneous recurrent seizures. We investigated the effect of Li/pilocarpine-induced SE on phosphorylation of the NMDA receptor in rat hippocampus. Phosphorylation of NR1 by PKC on Ser890 was decreased to 45% of control values immediately following 1 h of SE. During the first 3 h following the termination of SE, phosphorylation of Ser890 increased 4-fold before declining to control values by 24 h. Phosphorylation of NR1 by PKA was also depressed relative to controls immediately following SE and transiently increased above control values upon the termination of SE. SE was accompanied by a general increase in tyrosine phosphorylation of hippocampal proteins that lasted for several hours following the termination of seizures. Tyrosine phosphorylation of the NR2A and NR2B subunits of the NMDAR increased 3-4-fold over control values during SE, continued to increase during the first hour following SE and then declined to control levels by 24 h. SE resulted in the activation of Src and Pyk2 associated with the postsynaptic apparatus, suggesting a role for these enzymes in the SE-induced increase in tyrosine phosphorylation. Changes in phosphorylation of the NMDA receptor may play a role in the pathophysiological consequences of SE.
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PMID:Changes in phosphorylation of the NMDA receptor in the rat hippocampus induced by status epilepticus. 1574 56

The administration of lithium followed by pilocarpine induces status epilepticus (SE) that produces neurodegeneration and the subsequent development of spontaneous recurrent seizures. We have reported that tyrosine phosphorylation of the NMDA receptor is elevated over controls for several hours following 60 min of SE. In the current study, we assessed the temporal relationship between tyrosine phosphorylation of the NMDA receptor and the onset of SE. SE was induced using the Li/pilocarine model and phosphorylation of the NMDA receptor subunits NR2A and NR2B determined. Tyrosine phosphorylation of the NMDAR remained unchanged prior to the onset of SE and increased gradually thereafter. The onset of SE was accompanied by activation of Src-family tyrosine kinases and Pyk2 in the post-synaptic density, consistent with a role for these enzymes in SE-induced tyrosine phosphorylation. The results indicate that tyrosine phosphorylation of the NMDAR closely parallels the activation of Src-family kinases and follows, rather than precedes, the onset of SE.
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PMID:Increase in tyrosine phosphorylation of the NMDA receptor following the induction of status epilepticus. 1660 May 5

Pilocarpine-induced status epilepticus (SE) causes widespread tyrosine phosphorylation in the brain. It has been postulated that this intracellular signal may mediate potentially epileptogenic changes in the morphology and physiology of particular brain regions, including the hippocampus. The present study evaluated the effects of herbimycin A, a protein tyrosine kinase (PTK) inhibitor, over the acute (during which intense biochemical and electrophysiological activation occurs) and the chronic phase (characterized by spontaneous and recurrent epileptic seizures and the presence of synaptic reorganization, e.g., mossy fiber sprouting) of the pilocarpine model of epilepsy. The administration of a single dose of 1.74 nmol of herbimycin A (i.c.v., 5 microL) 5 min after the onset of SE did not change the acute behavioral manifestation of seizures despite significantly decreasing c-Fos immunoreactivity in different areas of the hippocampus and of the limbic cortex. Herbimycin-treated animals developed spontaneous recurrent seizures, as did control animals, with a similar latency for the appearance of the first seizure and similar seizure frequency. Neo-Timm staining revealed that all animals experiencing SE, regardless of whether or not injected with herbimycin, showed aberrant mossy fiber sprouting in the supragranular region of the dentate gyrus. Herbimycin did not obviously affect neuronal cell death as evaluated in Nissl-stained sections. These results indicate that the PTK blockade achieved with the current dose of herbimycin reduced the acute c-Fos expression but failed to alter the spontaneous seizure frequency or to attenuate the morphological modifications triggered by the SE.
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PMID:Effects of herbimycin A in the pilocarpine model of temporal lobe epilepsy. 1669 26


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