Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine leukemia inhibitory factor (LIF) modulates neuronal function during development and promotes neuronal survival after peripheral nerve injury, but little is known about LIF expression after cerebral ischemia. In the present study, the localization of LIF protein was immunohistochemically examined in rats after 3.5, 12, 24, 48, and 96 hours of reperfusion following 1.5 hours of middle cerebral artery occlusion (MCAO) induced by the intraluminal suture method. Double-staining immunohistochemistry with microtubule-associated protein-2 (MAP2), glial fibrillary acidic protein (GFAP), lectin histochemistry, and interleukin (IL) 6 was also performed. The sham group and immunosorption test did not show any clear LIF immunoreactivity. Definite LIF immunoreactivity was first detected after 12 hours of reperfusion in each of the brain regions examined: ischemic core, periinfarct region, and contralateral cortex. However, expression of LIF was most prominent in the periinfarct region at each time point, peaked at 24 hours, and then gradually declined until 96 hours of reperfusion. Some LIF-positive neurons in the periinfarct region expressed IL-6. At 96 hours of reperfusion, GFAP-labeled astrocytes around the infarct core also expressed LIF protein. Induction of LIF mRNA and protein was also confirmed by reverse transcription polymerase chain reaction and western blot analysis, respectively. These findings suggest that LIF expression in ischemically threatened neurons may reflect a repair or defense mechanism against the ischemic insult.
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PMID:Immunohistochemical detection of leukemia inhibitory factor after focal cerebral ischemia in rats. 1077 10

Interleukin-6 (IL-6) is pleiotropic cytokine involved in many central nervous system disorders including stroke, and elevated serum IL-6 has been found in acute stroke patients. IL-6 is implicated in the inflammation, which contributes to both injury and repair process after cerebral ischemia. However, IL-6 is one of the neurotrophic cytokines sharing a common receptor subunit, gp130, with other neurotrophic cytokines, such as leukemia inhibitory factor (LIF) and ciliary neurotrophic factor. The expression of IL-6 is most prominently identified in neurons in the peri-ischemic regions, and LIF expression shows a similar pattern. The direct injection of these cytokines into the brain after ischemia can reduce ischemic brain injury. The cytokine receptors are localized on the neuron surface, suggesting that neurons are the cytokine target. The major IL-6 downstream signaling pathway is JAK-STAT, and Stat3 activation occurs mainly in neurons during postischemic reperfusion. Further investigation is necessary to clarify the exact role of Stat3 signaling in neuroprotection. Taken together, the information suggests that IL-6 plays a double role in cerebral ischemia, as an inflammatory mediator during the acute phase and as a neurotrophic mediator between the subacute and prolonged phases.
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PMID:Ambivalent aspects of interleukin-6 in cerebral ischemia: inflammatory versus neurotrophic aspects. 1901 68

The discovery of the tissue-protective activities of erythropoietin (EPO) has underlined the importance of some cytokines in tissue-protection, repair, and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30). We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes), followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2). To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO) in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments.
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PMID:Definition of a Family of Tissue-Protective Cytokines Using Functional Cluster Analysis: A Proof-of-Concept Study. 2467 26