The P2X4 receptor is required for neuroprotection via ischemic preconditioning

Tomohiko Ozaki, Rieko Muramatsu, Miwa Sasai, Masahiro Yamamoto, Yoshiaki Kubota, Toshiyuki Fujinaka, Toshiki Yoshimine, Toshihide Yamashita

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


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.

Original languageEnglish
Article number25893
JournalScientific reports
Publication statusPublished - 2016 May 13

ASJC Scopus subject areas

  • General


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