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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numberENEURO.0474-19.2020
JournaleNeuro
Volume7
Issue number2
DOIs
Publication statusPublished - 2020
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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