title: PDGFR-β as a positive regulator of tissue repair in a mouse model of focal cerebral ischemia.
abstract: Although platelet-derived growth factors (PDGFs) and receptors (PDGFRs) are abundantly expressed in the central nervous system, their functions largely remain elusive. We investigated the role of PDGFR-β in tissue responses and functional recovery after photothrombolic middle cerebral artery occlusion (MCAO). In the normal adult mouse brain, PDGFR-β was mainly localized in neurons and in pericyte/vascular smooth muscle cells (PC/vSMCs). From 3 to 28 days after MCAO, postnatally induced systemic PDGFR-β knockout mice (Esr-KO) exhibited the delayed recovery of body weight and behavior, and larger infarction volume than controls. In Esr-KO, PC/vSMC coverage was decreased and vascular leakage of infused fluorescent-labeled albumin was extensive within the ischemic lesion, but not in the uninjured cerebral cortex. Angiogenesis levels were comparable between Esr-KO and controls. In another PDGFR-β conditional KO mouse (Nestin-KO), PDGFR-β was deleted in neurons and astrocytes from embryonic day 10.5, but was preserved in PC/vSMCs. After MCAO, vascular leakage and infarction volume in Nestin-KO were worse than controls, but partly improved compared with Esr-KO. Astroglial scar formation in both Esr-KO and Nestin-KO was similarly reduced compared with controls after MCAO. These data suggested that PDGFR-β signaling is crucial for neuroprotection, endogenous tissue repair, and functional recovery after stroke by targeting neurons, PC/vSMCs, and astrocytes.
authors.affiliation: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ishii
authors.forename: Guihua
authors.initials: G
authors.lastname: Xu
authors.forename: Thanh Chung
authors.initials: TC
authors.lastname: Dang
authors.forename: Takeru
authors.initials: T
authors.lastname: Hamashima
authors.forename: Takako
authors.initials: T
authors.lastname: Matsushima
authors.forename: Seiji
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hattori
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Takatsuru
authors.forename: Junichi
authors.initials: J
authors.lastname: Nabekura
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sasahara
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D002199:Capillary Permeability; D049109:Cell Proliferation; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D020797:Receptor, Platelet-Derived Growth Factor beta