The P2X4 receptor is required for neuroprotection via ischemic preconditioning

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...

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Veröffentlicht in:Scientific reports 2016-05, Vol.6 (1), p.25893-25893, Article 25893
Hauptverfasser: Ozaki, Tomohiko, Muramatsu, Rieko, Sasai, Miwa, Yamamoto, Masahiro, Kubota, Yoshiaki, Fujinaka, Toshiyuki, Yoshimine, Toshiki, Yamashita, Toshihide
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container_title Scientific reports
container_volume 6
creator Ozaki, Tomohiko
Muramatsu, Rieko
Sasai, Miwa
Yamamoto, Masahiro
Kubota, Yoshiaki
Fujinaka, Toshiyuki
Yoshimine, Toshiki
Yamashita, Toshihide
description 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.
doi_str_mv 10.1038/srep25893
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subjects 38/61
42/109
631/378
64/60
692/617
82/51
Humanities and Social Sciences
multidisciplinary
Science
title The P2X4 receptor is required for neuroprotection via ischemic preconditioning
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