%0 Journal Article %A Tomoya Shibahara %A Tetsuro Ago %A Kuniyuki Nakamura %A Masaki Tachibana %A Yoji Yoshikawa %A Motohiro Komori %A Kei Yamanaka %A Yoshinobu Wakisaka %A Takanari Kitazono %T Pericyte-Mediated Tissue Repair through PDGFRβ Promotes Peri-Infarct Astrogliosis, Oligodendrogenesis, and Functional Recovery after Acute Ischemic Stroke %D 2020 %R 10.1523/ENEURO.0474-19.2020 %J eneuro %P ENEURO.0474-19.2020 %V 7 %N 2 %X 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 astrogliosis, accompanied by increased STAT3 phosphorylation, was attenuated in Pdgfrb+/– mice. Pericyte-conditioned 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 myelination, 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. %U https://www.eneuro.org/content/eneuro/7/2/ENEURO.0474-19.2020.full.pdf