title: Induction of Perivascular Neural Stem Cells and Possible Contribution to Neurogenesis Following Transient Brain Ischemia/Reperfusion Injury.
abstract: Recent therapeutic advances have increased the likelihood of recanalizing the obstructed brain arteries in patients with stroke. Therefore, it is important to understand the fate of neural cells under transient ischemia/reperfusion injury. Accumulating evidence shows that neurogenesis occurs in perivascular regions following brain injury, although the precise mechanism and origin of these newborn neurons under transient ischemia/reperfusion injury remain unclear. Using a mouse model of transient brain ischemia/reperfusion injury, we found that neural stem cells (NSCs) develop within injured areas. This induction of NSCs following ischemia/reperfusion injury was observed even in response to nonlethal ischemia, although massive numbers of NSCs were induced by lethal ischemia. Immunohistochemical and immunoelectron microscopic studies indicated that platelet-derived growth factor receptor beta-positive (PDGFRβ+) pericytes within injured areas following nonlethal ischemia began to express the NSC marker nestin as early as 3 days after transient ischemia/reperfusion. Some PDGFRβ+pericytes expressed the immature neuronal marker doublecortin at day 7. These findings indicate that brain pericytes are a potential source of the perivascular NSCs that generate neuronal cells under lethal and nonlethal ischemic conditions following transient ischemia/reperfusion. Thus, brain pericytes might be a target for neurogenesis mediation in patients with nonlethal and lethal ischemia following transient ischemia/reperfusion injury.
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, 663-8501, Hyogo, Japan.|Department of Anesthesiology, Osaka Dental University, 1-5-17 Otemae, Chuo-ku, Osaka, 540-0008, Osaka, Japan.
authors.forename: Masayo
authors.initials: M
authors.lastname: Nakata
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, 663-8501, Hyogo, Japan. nakagomi@hyo-med.ac.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagomi
authors.affiliation: Multi-Modal Microstructure Analysis Unit, RIKEN CLST-JEOL Collaboration Center, RIKEN Center for Life Science Technologies, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Hyogo, Japan.
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Maeda
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, 663-8501, Hyogo, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakano-Doi
authors.affiliation: Department of Anesthesiology, Osaka Dental University, 1-5-17 Otemae, Chuo-ku, Osaka, 540-0008, Osaka, Japan. momota@cc.osaka-dent.ac.jp.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Momota
authors.affiliation: Institute for Advanced Medical Sciences, Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, 663-8501, Hyogo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001921:Brain / Q000503:physiopathology / Q000648:ultrastructure; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death; D042783:Endothelial Cells / Q000648:ultrastructure; D008297:Male; D051379:Mice; D064231:Nestin / Q000378:metabolism; D058953:Neural Stem Cells / Q000378:metabolism / Q000502:physiology*; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology; D020286:Pericytes / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology
chemical_list: C577485:Nes protein, mouse; D064231:Nestin; D020797:Receptor, Platelet-Derived Growth Factor beta
keywords: Ischemia/reperfusion; Neural stem cells; Neurogenesis; Pericyte; Stroke