| First Author | Shibahara T | Year | 2020 |
| Journal | eNeuro | Volume | 7 |
| Issue | 2 | PubMed ID | 32046974 |
| Mgi Jnum | J:289180 | Mgi Id | MGI:6431162 |
| Doi | 10.1523/ENEURO.0474-19.2020 | Citation | Shibahara T, et al. (2020) Pericyte-Mediated Tissue Repair through PDGFRbeta Promotes Peri-Infarct Astrogliosis, Oligodendrogenesis, and Functional Recovery after Acute Ischemic Stroke. eNeuro 7(2):ENEURO.0474-19.2020 |
| abstractText | 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 beta (PDGFRbeta)-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 PDGFRbeta may promote functional recovery through enhancement of peri-infarct oligodendrogenesis as well as astrogliosis after acute ischemic stroke. |
