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)

Although numerous studies have demonstrated the neurotrophic capacity of gp130 cytokines, it remains unclear whether endogenously expressed cytokines actually function in a direct neuromodulatory manner. Therefore, using the lithium-pilocarpine status epilepticus model, we performed a detailed in situ hybridization time-course study of five gp130 cytokines (interleukin [IL]-6, leukemia inhibitory factor [LIF], IL-11, oncostatin-m [OSM], and ciliary neurotrophic factor), gp130, and the receptors of the cytokines we found to be induced (IL-6 receptor [IL-6R], LIF receptor [LIF-R], and IL-11 receptor [IL-11R]). Additionally, to further understand the regulation of these cytokines, we compared their expression with the pattern of neuronal degeneration and microglial activation. Under control conditions, all cytokines, except LIF, exhibited faint to moderate expression in hippocampal principal layers. After seizure, IL-6, LIF, and IL-11 exhibited a rapid, robust, and transient upregulation in non-principal cells. LIF also exhibited a remarkably early and transient induction in the granule cell layer of the dentate gyrus. OSM exhibited only a mild and inconsistent induction. All receptors examined were strongly expressed only in hippocampal principal layers under control conditions. A mild and late induction of the IL-6R, LIF-R, and IL-11R occurred after seizure with a scattered distribution. A progressive and chronic induction of gp130 was observed in cells that appeared to be associated with blood vessels. Degeneration of hilar interneurons and CA1 pyramidal cells was early and progressive. Granule neurons of the dentate gyrus, however, exhibited a delayed and precipitous pattern of degeneration, specifically in the lateral portion of the superior blade. Microglial activation was maximal 24-48 h post-seizure. We speculate that gp130 cytokines play a paracrine, neuromodulatory role in the hippocampus since both before and after seizure, principal cells appear to be the major cell type expressing the receptors for these cytokines. Furthermore, we suggest that activity-dependent mechanisms may be involved in the regulation of cytokines expressed early, and that relatively late occurring cytokine expression may be elicited by injury-related stimuli.
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PMID:Spatiotemporal distribution of gp130 cytokines and their receptors after status epilepticus: comparison with neuronal degeneration and microglial activation. 1461

Numerous studies have investigated the expression of various cytokine families in the CNS after brain injury. The gp130 or interleukin (IL)-6-type cytokines have received a great deal of focus, and it is clear that they exhibit an acute and robust upregulation in various brain injury models. We are interested to determine, however, whether endogenously expressed cytokines in the CNS act in a direct neuromodulatory manner. In an accompanying study, we examined the expression of five gp130 cytokines and their receptors in the lithium-pilocarpine model of status epilepticus. We follow up that study here by trying to determine if gp130 signal transduction occurs in hippocampal principal neurons after seizure. Therefore, using the expression of suppressors of cytokine signaling (SOCS)-1 and -3 as indices of gp130 signal transduction, we performed a detailed in situ hybridization seizure time-course study in the adult rat hippocampus. For comparison, we also examined SOCS-2, which is involved in insulin-like growth factor signaling. We found that while SOCS-1 and -3 were faintly expressed under basal conditions, only SOCS-3 exhibited a rapid, robust, and transient induction. This occurred first in non-principal cells, which appeared to be glial, peaking at approximately 12 h post-seizure. Subsequently, a robust induction of SOCS-3 occurred in pyramidal and granule neurons, peaking at approximately 24 h. SOCS-2 displayed a relatively higher level of basal expression, particularly in CA3, and a mild and transient downregulation by 24 h. These findings corroborate the hypothesis that seizure-induced gp130 cytokines play a direct neuromodulatory role in the hippocampus. Since in our previous study we did not detect cytokine receptor expression in non-principal cells, it is unclear what elicits SOCS-3 expression in this population.
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PMID:Differential expression of suppressors of cytokine signaling-1, -2, and -3 in the rat hippocampus after seizure: implications for neuromodulation by gp130 cytokines. 1461 1