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Publication : The P2X4 receptor is required for neuroprotection via ischemic preconditioning.

First Author  Ozaki T Year  2016
Journal  Sci Rep Volume  6
Pages  25893 PubMed ID  27173846
Mgi Jnum  J:259935 Mgi Id  MGI:6102053
Doi  10.1038/srep25893 Citation  Ozaki T, et al. (2016) The P2X4 receptor is required for neuroprotection via ischemic preconditioning. Sci Rep 6:25893
abstractText  Ischemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance.
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