Invivo molecular mechanism and micro morphology of brain diseases in mice

• Project/Area Number: 24659578
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: KANNO Iwao 独立行政法人放射線医学総合研究所, 分子イメージング研究センター, 主任研究員 (10360356)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: PET / 低酸素飼育マウス / TSPO発現 / インテグリン発現 / 11C-PK11195 / 64Cu-RAFT-RGD / オートラジオグラフィ / 免疫染色 / 低酸素飼育 / PK11195 / RAFT-RGD / 中大脳動脈閉塞モデル / マウス / 脳虚血 / 脳血流量 / 虚血炎症 / TSPOマーカー / 中枢性ベンゾジアゼピン受容体

Research Abstract

We evaluated tissue pathophysiology and angiogenesis in the brain induced by hypoxia in mouse. B6 mice kept in 8-9% oxygen chamber for 0, 4, 7, 10, 14 days. Using PET, the TSPO emergence in the brain was estimated by employing[C11]PK11195 (PK), and the endothelium integrin was estimated by emplying [Cu64]RAFT-RDG (RDG). Autoradiography (ARG) was performed after RDG-PET. PK-PET revealed the SUV was peaked at 4th day, suggesting that microglia was maximally activated at 4th day. On the otherhand, RDG-PET was difficult to evaluate the maximum peak date of radioactivity in the brain due to too little entrance of the RDG through BBB. RDG-ARG revealed radioactivity in the brain parenchymal tissue only in the 14th day, suggesting angiogenesis was occurred at least 14th day, however, it is not clear whether angiogenesis appeared earlier than 14th day.

Research Products

• [Journal Article] Changes in cortical microvasculature during misery perfusion measured by two-photon laser scanning microscopy. (2014)
  • Author(s): Tajima Y, Takuwa H, Kokuryo D, Kawaguchi H, Seki C, Masamoto K, Ikoma Y, Taniguchi J, Aoki I, Tomita Y, Suzuki N, Kanno I, Saeki N, Ito H.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 34 Issue: 8 Pages: 1363-1372
  • DOI: 10.1038/jcbfm.2014.91
  • Peer Reviewed / Open Access
• [Journal Article] Microvascular sprouting, extension, and creation of new capillary connections with adaptation of the neighboring astrocytes in adult mouse cortex under chronic hypoxia (2014)
  • Author(s): Masamoto K, Kanno I, 他8名
  • Journal Title: J Cereb Blood Flow Metab Volume: 34 Pages: 325-31
  • Peer Reviewed
• [Journal Article] Reproducibility of measuring cerebral blood flow by laser-Doppler flowmetry in mice (2014)
  • Author(s): Yosuke Tajima, Hiroyuki Takuwa, Hiroshi Kawaguchi, Kazuto Masamoto, Yoko Ikoma, Chie Seki, Junko Taniguchi, Iwao Kanno, Naokatsu Saeki, Hiroshi Ito
  • Journal Title: Frontiers in Bioscience Elite Edition Volume: 6E Pages: 62-68
  • Peer Reviewed
• [Journal Article] Evaluation of Rho-Kinase Activity in Mice Brain Using N-[(11)C]Methyl-hydroxyfasudil with Positron Emission Tomography. (2014)
  • Author(s): Junko Taniguchi, Chie Seki, Hiroyuki Takuwa, Hiroshi Kawaguchi, Yoko Ikoma, Masayuki Fujinaga, Iwao Kanno, Ming-Rong Zhang, Satoshi Kuwabara, Hiroshi Ito
  • Journal Title: Molecular imaging and biology Volume: 16 Pages: 395-402
  • Peer Reviewed
• [Journal Article] Biodistribution and radiation dosimetry in humans of [11C]FLB 457, a positron emission tomography ligand for the extrastriatal dopamine D2 receptor (2014)
  • Author(s): Yasuyuki Kimura, Hiroshi Ito, Takahiro Shiraishi, Hironobu Fujiwara, Fumitoshi Kodaka, Harumasa Takano, Hitoshi Shimada, Iwao Kanno, Tetsuya Suhara
  • Journal Title: Nuclear Medicine and Biology Volume: 41 Pages: 102-105
  • Peer Reviewed
• [Journal Article] Novel system using microliter order sample volume for measuring arterial radioactivity concentrations in whole blood and plasma for mouse PET dynamic study (2013)
  • Author(s): Kimura A, Kanno I, 他8名
  • Journal Title: Phys Med Biol Volume: 58 Pages: 7889-7903
  • Peer Reviewed
• [Journal Article] Measuring the vascular diameter of brain surface and parenchymal arteries in awake mouse (2013)
  • Author(s): Sekiguchi Y, Masamoto K, Takuwa H, Kawaguchi H, Kanno I, Ito H, Tomita Y, Itoh Y, Suzuki N, Sudo R, Tanishita K
  • Journal Title: Advances in experimental medicine and biology Volume: 789 Pages: 419-25
  • DOI: 10.1007/978-1-4614-7411-1_56
  • ISBN: 9781461472568, 9781461474111
  • Peer Reviewed
• [Journal Article] “Hypoxia-induced cerebral angiogenesis in mouse cortex with two-photon microscopy.” (2013)
  • Author(s): Masamoto K, Takuwa H, Tomita Y, Toriumi H, Unekawa M, Taniguchi J, Kawaguchi H, Itoh Y, Suzuki N, Ito H, Kanno I.
  • Journal Title: Adv Exp Med Biol. Volume: 789 Pages: 15-20
  • DOI: 10.1007/978-1-4614-7411-1_3
  • ISBN: 9781461472568, 9781461474111
  • Peer Reviewed
• [Journal Article] Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex. (2013)
  • Author(s): Hotta, H., Masamoto,K., Uchida,S.,Sekiguchi,Y., Takuwa,H., Kawaguchi,H., Shigemoto,K., Sudo,R., Tanishita,K., Ito,H. and Kanno,I.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 9 Issue: 9 Pages: 1440-7
  • DOI: 10.1038/jcbfm.2013.92
  • Peer Reviewed
• [Journal Article] Microvascular sprouting, extension, and creation of new capillary connections with adaptation of the neighboring astrocytes in adult muose cortex under chronic hypoxia (2013)
  • Author(s): Kazuto Masamoto, Hiroyuki Takuwa, Chie Seki, Junko Taniguchi, Yoshiaki Itoh, Yutaka Tomita, Haruki Toriumi, Miyuki Unekawa, Hiroshi Kawaguchi, Hiroshi Ito, Norihiro Suzuki, Iwao Kanno
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 33 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Novel system using microliter order sample volume for measuring arterial radioactivity concentrations in whole blood and plasma for mouse PET dynamic study (2013)
  • Author(s): Yuichi Kimura, Chie Seki, Nobuya Hashizume, Takashi Yamada, Hidekatsu Wakizaka, Takahiro Nishimoto, Kentaro Hatano, Keishi Kitamura, Hiroshi Toyama, Iwao Kanno
  • Journal Title: Physics in Medicine and Biology Volume: 58 Pages: 7889-7903
  • Peer Reviewed
• [Journal Article] Hemodynamic changes during neural deactivation in awake mice: A measurement by laser-Doppler flowmetry in crossed cerebellar diaschisis (2013)
  • Author(s): Hiroyuki Takuwa, Yousuke Tajima, Daisuke Kokuryo, Tetsuya Matsuura, Hiroshi Kawaguchi, Kazuto Masamoto, Jyunko Taniguchi, Youko Ikoma, Chie Seki, Ichio Aoki, Yutaka Tomita, Norihiro Suzuki, Iwao Kanno, Hiroshi Ito
  • Journal Title: Brain Research Volume: 1537 Pages: 350-355
  • Peer Reviewed
• [Journal Article] Layer-specific dilation of penetrating arteries induced by stimulation of the nucleus basalis of Meynert in the mouse frontal cortex (2013)
  • Author(s): Harumi Hotta, Kazuto Masamoto, Sae Uchida, Yuta Sekiguchi, Hiroyuki Takuwa, Hiroshi Kawaguchi, Ryo Sudo, Kazuo Tanishita, Hiroshi Ito, Iwao Kanno, et.al
  • Journal Title: Journal of Cerebral Blood Flow and Metabolism Volume: 33 Pages: 1440-1447
  • Peer Reviewed
• [Journal Article] Measuring the vascular diameter of brain surface and parenchymal arteries in awake mouse (2013)
  • Author(s): Yuta Sekiguchi, Kazuto Masamoto, Hiroyuki Takuwa, Hiroshi Kawaguchi, Iwao Kanno, Hiroshi Ito, Yutaka Tomita, Yoshiaki Itoh, Norihiro Suzuki, Ryo Sudo, Kazuo Tanishita
  • Journal Title: Advances in Experimental Medicine and Biology Volume: 789 Pages: 419-425
  • Peer Reviewed
• [Journal Article] Hypoxia-Induced Cerebral Angiogenesis in Mouse Cortex with Two-Photon Microscopy (2013)
  • Author(s): Kazuto Masamoto, Hiroyuki Takuwa, Yutaka Tomita, Haruki Toriumi, Miyuki Unekawa, Jyunko Taniguchi, Hiroshi Kawaguchi, Yoshiaki Itoh, Norihiro Suzuki, Hiroshi Ito, Iwao Kanno
  • Journal Title: Advances in Experimental Medicine and Biology Volume: 789 Pages: 15-20
  • Peer Reviewed
• [Journal Article] “Long-term adaptation of cerebral hemodynamic response to somatosensory stimulation during chronic hypoxia in awake mice.” (2013)
  • Author(s): Takuwa H, Masamoto K, Yamazaki K, Kawaguchi H, Ikoma Y, Tajima Y, Obata T, Tomita Y, Suzuki N, Kanno I, Ito H.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 33(5) Issue: 5 Pages: 774-779
  • DOI: 10.1038/jcbfm.2013.16
  • Peer Reviewed
• [Journal Article] Potassium-induced cortical spreading depression bilaterally suppresses the electroencephalogram but only ipsilaterally affects red blood cell velocity in intraparenchymal capillaries (2013)
  • Author(s): Unekawa M, Tomita Y, Toriumi H, Masamoto K, Kanno I, Suzuki N
  • Journal Title: J Neurosci Res Volume: 91 Pages: 578-84
  • Peer Reviewed
• [Journal Article] 3D analysis of intracortical microvasculature during chronic hypoxia in mouse brains (2013)
  • Author(s): Yoshihara K, Takuwa H, Kanno I, Okawa S, Yamada Y, Masamoto K
  • Journal Title: Adv Exp Med Biol Volume: 765 Pages: 357-63
  • Peer Reviewed
• [Journal Article] Dynamic two-photon imaging of cerebral microcirculation using fluorescently labeled red blood cells and plasma (2013)
  • Author(s): Masamoto K, Kawaguchi H, Ito H, Kanno I
  • Journal Title: Adv Exp Med Biol Volume: 765 Pages: 163-8
  • Peer Reviewed
• [Journal Article] Hemodynamic changes during somatosensory stimulation in awake and isoflurane-anesthetized mice measured by laser-Doppler flowmetry (2012)
  • Author(s): Takuwa H, Matsuura T, Obata T, Kawaguchi H, Kanno I, Ito H
  • Journal Title: Brain Res Volume: 1472 Pages: 107-12
  • Peer Reviewed
• [Presentation] 覚醒マウス脳表における神経活動および脳血流変化の同時計測システムの構築 (2013)
  • Author(s): 田桑弘之,菅野巖, 他5名
  • Organizer: レーザー学会第452回研究会「ニューロフォトニクス」,日本レーザー学会
  • Year and Date: 2013-11-29
• [Presentation] 二光子顕微鏡でのCBV測定 (2013)
  • Author(s): 川口拓之,菅野巖, 他5名
  • Organizer: 第3回核医学画像解析研究会,核医学画像解析研究会
  • Year and Date: 2013-11-25
• [Presentation] 脳賦活および脳機能抑制による細動脈、毛細血管、細静脈の血管径変化 (2013)
  • Author(s): 田桑弘之,菅野巖, 他5名
  • Organizer: 第25回日本脳循環代謝学会総会,日本脳循環代謝学会
  • Year and Date: 2013-11-02
• [Presentation] Reduced Response in Cortical Penetrating Artery but Sustained Response in Cortical Surface Artery to Whisker Stimulation in Chronic Hypoxia Mice (2013)
  • Author(s): Kanno I, 他11名
  • Organizer: Brain & BrainPET 2013
  • Place of Presentation: ISCBFM,上海
  • Year and Date: 2013-05-23
• [Presentation] Hemodynamic changes in crossed cerebellar diaschisis measured by Laser-Doppler flowmetry in awake mice (2013)
  • Author(s): Takuwa H, Kanno I, 他8名
  • Organizer: Brain & Brain PET 2013
  • Place of Presentation: ISCBFM,上海
  • Year and Date: 2013-05-23
• [Presentation] Measuring the vascular diameter of brain surface arteries and parenchymal arterioles in awake mouse, by ；2012-08-19～2012-08-23にベルギーで開催のISOTT会議。 (2012)
  • Author(s): Yuta Sekiguchi、Kazuto Masamoto、Hiroyuki Takuwa、Hiroshi Kawaguchi、Iwao Kanno、Hiroshi Ito、Yutaka Tomita、Norihiro Suzuki、Ryo Sudo、Kazuo Tanishita
  • Organizer: 2012年国際酸素組織移行学会（ISOTT2012)
  • Place of Presentation: Bruges
• [Presentation] 持続的低酸素暴露マウスの脳におけるFDG測定 (2012)
  • Author(s): 菅野 巖、田桑 弘之、関 千江、正本 和人、谷口 順子、川口 拓之、生駒 洋子、脇坂 秀克、伊藤 浩
  • Organizer: 第52回日本核医学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] 脳機能抑制による局所脳血流の変化 –Crossed cerebellar diaschisisモデルマウスにおけるLDF計測- (2012)
  • Author(s): 田桑 弘之、川口 拓之、正本 和人、谷口 順子、菅野 巖、伊藤 浩
  • Organizer: 第24回日本脳循環代謝学会総会
  • Place of Presentation: 広島市
• [Presentation] 麻酔下マウスにおける大脳皮質性拡延性抑制誘発時の脳表動静脈および毛細血管の口径と脳血流の変化、 (2012)
  • Author(s): 畝川 美悠紀、冨田 裕、鳥海 春樹、長田 高志、正本 和人、川口 拓之、菅野 巖、鈴木 則宏*
  • Organizer: 第24回日本脳循環代謝学会総会
  • Place of Presentation: 広島市
• [Presentation] 慢性低酸素飼育下マウスの大脳皮質体性感覚野における脳表動脈と穿通動脈のひげ刺激応答 (2012)
  • Author(s): 菅野 巖、関口 優太、田桑 弘之、正本 和人、川口 拓之、谷口 順子、冨田 裕、須藤 亮*、鈴木 則宏*、谷下 一夫*、伊藤 浩
  • Organizer: 第24回日本脳循環代謝学会総会
  • Place of Presentation: 広島市
• [Presentation] 覚醒マウス脳表における神経活動および脳血流変化の同時計測システムの構築
  • Author(s): 田桑 弘之, 西野 明日香, 川口 拓之, 正本 和人, 松浦 哲也, 菅野 巖, 伊藤 浩
  • Organizer: レーザー学会第４５２回研究会
  • Place of Presentation: 東京
• [Presentation] 二光子顕微鏡てのCBV測定
  • Author(s): 川口拓之, 田桑 弘之, 谷口 順子, 正本 和人, 菅野 巖, 伊藤 浩
  • Organizer: 第3回核医学画像解析研究会
  • Place of Presentation: 秋田
• [Presentation] [11C]FLB 457によるPET測定の３機種間差
  • Author(s): 木村 泰之, 白石 貴博, 生駒 洋子, 高野 晴成, 高畑 圭輔, 小高 文聰, 藤原 広臨, 菅野 巖, 須原 哲也, 須原 哲也
  • Organizer: 第53回日本核医学会学術総会,
  • Place of Presentation: 福岡
• [Presentation] PETによるレセプター結合能測定における麻酔と拘束の影響
  • Author(s): 田桑 弘之, 前田 純, 徳永 正希, 脇坂 秀克, 生駒 洋子, 関 千江, 川口 拓之, 田島 洋佑, 谷口 順子, 菅野 巖, 伊藤 浩
  • Organizer: 第25回日本脳循環代謝学会総会
  • Place of Presentation: 札幌
• [Presentation] 脳賦活および脳機能抑制による細動脈、毛細血管、細静脈の血管径変化
  • Author(s): 田桑 弘之, 田島 洋佑, 川口 拓之, 谷口 順子, 正本 和人, 菅野 巖, 伊藤 浩
  • Organizer: 第25回日本脳循環代謝学会総会
  • Place of Presentation: 札幌
• [Presentation] 脳賦活および脳機能抑制による局所脳有効酸素拡散能変化の推定 −覚醒マウスにおける毛細血管径毎の検討−
  • Author(s): 伊藤 浩, 田桑 弘之, 川口 拓之, 田島 洋佑, 茨木 正信, 正本 和人, 菅野 巖
  • Organizer: 第25回日本脳循環代謝学会総会
  • Place of Presentation: 札幌
• [Presentation] Hemodynamic changes in crossed cerebellar diaschisis measured by Laser-Doppler flowmetry in awake mice
  • Author(s): Hiroyuki Takuwa, Yousuke Tajima, Hiroshi Kawaguchi, Jyunko Taniguchi, Youko Ikoma, Kazuto Masamoto, Chie Seki, Iwao Kanno, Hiroshi Ito
  • Organizer: XXIst International Symposium on Cerebral Blood Flow, Metabolism and Function & VIth International Conference on Quantification of Brain Function with PET
  • Place of Presentation: 上海
• [Presentation] Reduced Response in Cortical Penetrating Artery but Sustained Response in Cortical Surface Artery to Whisker Stimulation in Chronic Hypoxia Mice
  • Author(s): Iwao Kanno, Yuta Sekiguchi, Hiroyuki Takuwa, Kazuto Masamoto, Hiroshi Kawaguchi, Jyunko Taniguchi, Yutaka Tomita, Ryo Sudo, Kazuo Tanishita, Yoshiaki Itoh, Norihiro Suzuki, Hiroshi Ito
  • Organizer: XXIst International Symposium on Cerebral Blood Flow, Metabolism and Function & VIth International Conference on Quantification of Brain Function with PET
  • Place of Presentation: 上海
• [Presentation] 脳核医学と分子イメージング − 核医学を目指す若い人たちへのメーセージ
  • Author(s): 菅野 巖
  • Organizer: 第53回日本核医学会学術総会,
  • Place of Presentation: 福岡
  • Invited
• [Remarks] 招待講演(合計1件) 菅 野 巖、脳核医学と分子イメージング-核医学を目指す若い人たちへのメッセージ、特別講演、第53回日本核医学会学術総会、福岡市、2013-11-08
• [Remarks] 依頼原稿(合計1件) 菅 野 巖、PET今昔、巻頭言、Isotope News 722、2014
• [Remarks] 放射線医学総合研究所 研究領域活動
  • URL: http://www.nirs.go.jp/rd/index.shtml