title: Hypoxia-induced cerebral angiogenesis in mouse cortex with two-photon microscopy.
abstract: To better understand cellular interactions of the cerebral angiogenesis induced by hypoxia, a spatiotemporal dynamics of cortical microvascular restructuring during an exposure to continuous hypoxia was characterized with in vivo two-photon microscopy in mouse cortex. The mice were prepared with a closed cranial window over the sensory-motor cortex and housed in 8-9 % oxygen room for 2-4 weeks. Before beginning the hypoxic exposure, two-photon imaging of cortical microvasculature was performed, and the follow-up imaging was conducted weekly in the identical locations. We observed that 1-2 weeks after the onset of hypoxic exposure, a sprouting of new vessels appeared from the existing capillaries. An average emergence rate of the new vessel was 15 vessels per unit volume (mm(3)). The highest emergence rate was found in the cortical depths of 100-200 μm, indicating no spatial uniformity among the cortical layers. Further, a leakage of fluorescent dye (sulforhodamine 101) injected into the bloodstream was not detected, suggesting that the blood-brain barrier (BBB) was maintained. Future studies are needed to elucidate the roles of perivascular cells (e.g., pericyte, microglia, and astroglia) in a process of this hypoxia-induced angiogenesis, such as sprouting, growth, and merger with the existing capillary networks, while maintaining the BBB.
authors.affiliation: Center for Frontier Science and Engineering, University of Electro-Communications, 1-5-1 Chofugaoka, Chofu, 182-8585, Tokyo, Japan. masamoto@mce.uec.ac.jp.|Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan. masamoto@mce.uec.ac.jp.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Masamoto
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takuwa
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tomita
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Toriumi
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Unekawa
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Taniguchi
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Neurology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
authors.forename: Iwao
authors.initials: I
authors.lastname: Kanno
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D036641:Microscopy, Fluorescence, Multiphoton / Q000379:methods; D009044:Motor Cortex / Q000098:blood supply* / Q000378:metabolism / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D020286:Pericytes / Q000378:metabolism / Q000473:pathology
chemical_list: D010100:Oxygen