Pericyte-mediated tissue repair through PDGFRβ promotes peri-infarct astrogliosis, oligodendrogenesis, and functional recovery after acute ischemic stroke

Tomoya Shibahara, Tetsuro Ago, Kuniyuki Nakamura, Masaki Tachibana, Yoji Yoshikawa, Motohiro Komori, Kei Yamanaka, Yoshinobu Wakisaka, Takanari Kitazono

研究成果: Contribution to journalArticle査読

13 被引用数 (Scopus)

抄録

Post-stroke functional recovery can occur spontaneously during the subacute phase; however, how post-stroke fibrotic repair affects functional recovery is highly debated. Platelet-derived growth factor receptor β (PDGFRβ)-expressing pericytes are responsible for post-stroke fibrotic repair within infarct areas; therefore, we examined peri-infarct neural reorganization and functional recovery after permanent middle cerebral artery occlusion (pMCAO) using pericyte-deficient Pdgfrb+/– mice. Time-dependent reduction of infarct area sizes, i.e., repair, was significantly impaired in Pdgfrb+/– mice with recovery of cerebral blood flow (CBF) in ischemic areas attenuated by defective leptomeningeal arteriogenesis and intrainfarct angiogenesis. Peri-infarct astro-gliosis, accompanied by increased STAT3 phosphorylation, was attenuated in Pdgfrb+/– mice. Pericyte-condi-tioned medium (PCM), particularly when treated with platelet-derived growth factor subunit B (PDGFB) homodimer (PDGF-BB; PCM/PDGF-BB), activated STAT3 and enhanced the proliferation and activity of cultured astrocytes. Although peri-infarct proliferation of oligodendrocyte (OL) precursor cells (OPCs) was induced promptly after pMCAO regardless of intrainfarct repair, OPC differentiation and remyelination were significantly attenuated in Pdgfrb+/– mice. Consistently, astrocyte-CM (ACM) promoted OPC differentiation and myelina-tion, which were enhanced remarkably by adding PCM/PDGF-BB to the medium. Post-stroke functional recovery correlated well with the extent and process of intrainfarct repair and peri-infarct oligodendrogenesis. Overall, pericyte-mediated intrainfarct fibrotic repair through PDGFRβ may promote functional recovery through enhancement of peri-infarct oligodendrogenesis as well as astrogliosis after acute ischemic stroke.

本文言語英語
論文番号ENEURO.0474-19.2020
ジャーナルeNeuro
7
2
DOI
出版ステータス出版済み - 2020

All Science Journal Classification (ASJC) codes

  • 神経科学(全般)

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