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)

So far, microglial activation in cerebral ischemia has only been studied in different animal models. We have investigated the activation of microglial cells in human cerebral ischemia. As a marker for the activation of these "brain macrophages," we have used the macrophage inhibitor factor-related-proteins MRP-8 and MRP-14, which belong to the calcium binding S-100 protein family. The proteins can be detected on microglial cells in bacterial encephalitis and Alzheimer's disease but have so far not been studied in non-inflammatory diseases, in which microglial activation also occurs. Antibodies against MRP-8 and -14 detected ramified microglial cells within the first 3 days after cerebral infarction. Labeled cells were found selectively in the periinfarctional area. To support the notion that these cells belong to the locally activated resident microglial population, we studied their proliferation rate by staining the Ki-67 antigen with the antibody MIB-1. Double-labeling clearly showed that in the early phase of cerebral infarction microglial cells in the periinfarctional area express MRP-8 and -14 and also proliferate. Surprisingly, MRPs are expressed no longer than 3 days post infarction. This indicates that the activation of the resident microglia is an early step of tissue reaction after cerebral infarction. Additionally, we found evidence that microglial cells contribute to the population of phagocytes only during the first 3 days post infarction. The majority of lipid phagocytes found in the later stages are obviously recruited from the blood-borne macrophage pool.
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PMID:Expression of the S-100 proteins MRP-8 and -14 in ischemic brain lesions. 898 65

The tissue type plasminogen activator (t-PA) is a serine protease that is involved in neuronal plasticity and cell death induced by excitotoxins and ischemia in the brain. t-PA activity in the central nervous system is regulated through the activation of serine protease inhibitors (serpins) such as the plasminogen activator inhibitor (PAI-1), the protease nexin-1 (PN-1), and neuroserpin (NSP). Recently we demonstrated in vitro that PAI-1 produced by astrocytes mediates the neuroprotective effect of the transforming growth factor-beta1 (TGF-beta1) in NMDA-induced neuronal cell death. To investigate whether serpins may be involved in neuronal cell death after cerebral ischemia, we determined, by using semiquantitative RT-PCR and in situ hybridization, that focal cerebral ischemia in mice induced a dramatic overexpression of PAI-1 without any effect on PN-1, NSP, or t-PA. Then we showed that although the expression of PAI-1 is restricted to astrocytes, PN-1, NSP, and t-PA are expressed in both neurons and astrocytes. Moreover, by using semiquantitative RT-PCR and Western blotting, we observed that only the expression of PAI-1 was modulated by TGF-beta1 treatment via a TGF-beta-inducible element contained in the PAI-1 promoter (CAGA box). Finally, we compared the specificity of TGF-beta1 action with other members of the TGF-beta family by using luciferase reporter genes. These data show that TGF-beta and activin were able to induce the overexpression of PAI-1 in astrocytes, but that bone morphogenetic proteins, glial cell line-derived neutrophic factor, and neurturin did not. These results provide new insights into the regulation of the serpins/t-PA axis and the mechanism by which TGF-beta may be neuroprotective.
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PMID:Transforming growth factor-beta1 as a regulator of the serpins/t-PA axis in cerebral ischemia. 1042 56

Focal cerebral ischemia elicits a strong inflammatory response which readily participates in lipid oxygenation, edema formation, apoptotic cell death and tissue remodeling. Within these conditions, cytokines are key players of cell activation and are crucial for delayed mechanisms of ischemic damage. Mature IL-16 is an immunomodulatory cytokine, exerting CD4 dependent and independent effects and is characterized by chemotactic activity, induction of early gene phosphorylation, stimulation of pro-inflammatory IL-1beta, IL-6, TNFalpha expression in monocytic cells and also modulates apoptosis. We have now analyzed expression of IL-16 in 20 brains of patients following focal cerebral infarctions (FCI, n=20). Compared to normal control brains (n=3), IL-16 was expressed by infiltrating immune cells such as neutrophils, CD8+ lymphocytes and activated CD68+ microglia/macrophages accumulating in lesion associated reactive zones and in peri-vascular regions. IL-16+ cells accumulated significantly (P<0.0001) in the necrotic lesion and at bordering peri-lesional areas at day 1-2 reaching maximum levels at day 3-4 (P<0.0001). Also, peri-vascular IL-16+ cells reached maximum levels at day 3-4 (P<0.0001) following infarction and decreased after several weeks. During the early microglial activation period, IL-16+ microglia/macrophages coexpress the activation antigen MRP-8. The accumulation of IL-16+ granulocytes, IL-16+, CD8+ lymphocytes and activated IL-16+, CD68+, CD4- microglia/macrophages, early after infarction suggest a CD4 independent, paracrine role of IL-16 in the postinjury inflammatory response, such as recruitment and activation of immune cells leading to microvessel clustering and blood-brain barrier disturbance resulting in secondary damage.
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PMID:Human focal cerebral infarctions induce differential lesional interleukin-16 (IL-16) expression confined to infiltrating granulocytes, CD8+ T-lymphocytes and activated microglia/macrophages. 1124 37

Several reports have recently demonstrated a detrimental role of Toll-like receptors (TLR) in cerebral ischemia, while there is little information about the endogenous ligands which activate TLR-signaling. The myeloid related proteins-8 and-14 (Mrp8/S100A8; Mrp14/S100A9) have recently been characterized as endogenous TLR4-agonists, and thus may mediate TLR-activation in cerebral ischemia. Interestingly, not only TLR-mRNAs, but also Mrp8 and Mrp14 mRNA were found to be induced in mouse brain between 3 and 48 h after transient 1 h focal cerebral ischemia/reperfusion. Mrp-protein was expressed in the ischemic hemisphere, and co-labeled with CD11b-positive cells. To test the hypothesis that Mrp-signaling contributes to the postischemic brain damage, we subjected Mrp14-deficient mice, which also lack Mrp8 protein expression, to focal cerebral ischemia. Mrp14-deficient mice had significantly smaller lesion volumes when compared to wild-type littermates (130+/-16 mm(3) vs. 105+/-28 mm(3)) at 2 days after transient focal cerebral ischemia (1 h), less brain swelling, and a reduced macrophage/microglia cell count in the ischemic hemisphere. We conclude that upregulation and signaling of Mrp-8 and-14 contribute to neuroinflammation and the progression of ischemic damage.
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PMID:Mrp-8 and -14 mediate CNS injury in focal cerebral ischemia. 1983 55