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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concept of the neurovascular unit emphasizes that common signals and substrates underlie the physiology and pathophysiology of neuronal and endothelial compartments in brain. Recent data suggest that activation of the integrin-associated protein CD47 promotes neuronal cell death. Is it possible that CD47 may also negatively affect cerebral endothelial cells? Exposure of wild-type primary mouse cerebral endothelial cells to the CD47 ligand thrombospondin 1 (TSP-1) induced an increasing amount of cell death, whereas cytotoxicity was significantly decreased in cerebral endothelial cells derived from CD47 knockout mice. The specific CD47-activating peptide, 4N1K, similarly induced cell death in human brain microvascular endothelial cells. Promotion of inflammation was also involved because lower TSP-1 was able to up-regulate the adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Finally, CD47 signaling may suppress angiogenesis because 4N1K significantly inhibited endothelial cell migration and tube formation in vitro. We conclude that CD47 signaling can negatively affect the viability and function of cerebral endothelial cells, further supporting the notion that CD47 may be a potential neurovascular target for stroke and brain injury.
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PMID:Neurovascular effects of CD47 signaling: promotion of cell death, inflammation, and suppression of angiogenesis in brain endothelial cells in vitro. 1936 Sep

Neurovascular injury comprises a wide spectrum of pathophysiology that underlies the progression of brain injury after cerebral ischemia. Recently, it has been shown that activation of the integrin-associated protein CD47 mediates the development of blood-brain barrier injury and edema after cerebral ischemia. However, the mechanisms that mediate these complex neurovascular effects of CD47 remain to be elucidated. Here, we compare the effects of CD47 signaling in brain endothelial cells, astrocytes, and pericytes. Exposure to 4N1 K, a specific CD47-activating peptide derived from the major CD47 ligand thrombospondin-1, upregulated two major neurovascular mediators, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9), in brain endothelial cells and astrocytes. No changes were detected in pericytes. These findings may provide a potential mechanism for CD47-induced changes in blood-brain barrier homeostasis, and further suggest that CD47 may be a relevant neurovascular target in stroke.
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PMID:Induction of vascular endothelial growth factor and matrix metalloproteinase-9 via CD47 signaling in neurovascular cells. 2036 20