Chronic effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model

• Project/Area Number: 26861028
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Radiation science
• Research Institution: National Institute of Radiological Sciences
• Principal Investigator: Takuwa Hiroyuki 国立研究開発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, 研究員 (40508347)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 慢性低灌流 / 脳卒中 / モデル動物 / 二光子励起レーザー顕微鏡 / 小動物PET / PET / 二光子顕微鏡 / 病態モデルマウス / 脳血流 / 神経機能障害 / 神経細胞脱落 / 脳循環代謝障害 / 11C］flumazenil-PET

Outline of Final Research Achievements

In this study, we investigated the effects of chronic cerebral hypoperfusion on brain induced by a unilateral common carotid artery occlusion (UCCAO). As the first step of this study, we developed a misery perfusion mouse model using UCCAO and measured autoregulatory vasodilation with two-photon microscopy. The diameter of arterioles and capillaries during the resting state were increased 7 days after UCCAO. After UCCAO, autoregulatory vasodilation of arterioles during normocapnia was negatively correlated with a vasodilation during hypercapnia. The second step of this study was to investigate the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia. Neuronal density evaluated 28 days after UCCAO using [11C]flumazenil-PET and histology indicated no neurologic deficit in brain. Functional hyperemia induced by sensory stimulation was assessed using laser-Doppler flowmetry and became worse 28 days after UCCAO.

Research Products

• [Journal Article] Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model. (2016)
  • Author(s): Nishino A, Tajima Y, Takuwa H, Masamoto K, Taniguchi J, Wakizaka H, Kokuryo D, Urushihata T, Aoki I, Kanno I, Tomita Y, Suzuki N, Ikoma Y, Ito H.
  • Journal Title: Sci Rep Volume: 27 Pages: 25072-25072
  • DOI: 10.1038/srep25072
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dynamic flow velocity mapping from fluorescent dye transit times in the brain surface microcirculation of anesthetized rats and mice. (2016)
  • Author(s): Hoshikawa R, Kawaguchi H, Takuwa H, Ikoma Y, Tomita Y, Unekawa M, Suzuki N, Kanno I, Masamoto K.
  • Journal Title: Microcirculation Volume: 26 Pages: 416-425
  • DOI: 10.1111/micc.12285
  • Peer Reviewed
• [Journal Article] Vasodilation Mechanism of Cerebral Microvessels Induced by Neural Activation under High Baseline Cerebral Blood Flow Level Results from Hypercapnia in Awake Mice. (2015)
  • Author(s): Nishino A, Takuwa H, Urushihata T, Ito H, Ikoma Y, Matsuura T.
  • Journal Title: Microcirculation Volume: 22 Pages: 744-752
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] [(11)C]Raclopride binding in the striatum of minimally restrained and free-walking awake mice in a positron emission tomography study. (2015)
  • Author(s): Takuwa H, Maeda J, Ikoma Y, Tokunaga M, Wakizaka H, Uchida S, Kanno I, Taniguchi J, Ito H, Higuchi M
  • Journal Title: Synapse Volume: 69 Pages: 600-606
  • DOI: 10.1002/syn.21864
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Development of new optical imaging systems of oxygen metabolism and simultaneous measurement in hemodynamic changes using awake mice. (2014)
  • Author(s): Takuwa H, Matsuura T, Nishino A, Sakata K, Tajima Y, Ito H
  • Journal Title: J Neurosci Methods. Volume: 30 Pages: 9-15
  • DOI: 10.1016/j.jneumeth.2014.08.022
  • Peer Reviewed
• [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 Pages: 1363-1372
  • DOI: 10.1038/jcbfm.2014.91
  • Peer Reviewed / Open Access
• [Journal Article] Pial arteries respond earlier than penetrating arterioles to neural activation in the somatosensory cortex in awake mice exposed to chronic hypoxia: an additional mechanism to proximal integration signaling? (2014)
  • Author(s): Sekiguchi Y, Takuwa H, Kawaguchi H, Kikuchi T, Okada E, Kanno I, Ito H, Tomita Y, Itoh Y, Suzuki N, Sudo R, Tanishita K, Masamoto K.
  • Journal Title: Journal of Cerebral Blood Flow & Metabolism Volume: 34 Pages: 1761-1770
  • DOI: 10.1038/jcbfm.2014.140
  • Peer Reviewed / Open Access
• [Presentation] PET技術と生体光イメージング技術の融合と脳疾患研究 (2016)
  • Author(s): 田桑弘之
  • Organizer: JAEA放射光科学シンポジウム2016
  • Place of Presentation: 兵庫県 播磨
  • Year and Date: 2016-02-25
  • Invited
• [Presentation] フラビン蛍光イメージングへの血流の影響の補正法の検討 (2015)
  • Author(s): 漆畑拓弥
  • Organizer: ニューロフォトニクス
  • Place of Presentation: 東京
  • Year and Date: 2015-12-03
• [Presentation] DIAMETER CHANGES TO CEREBRAL BLOOD VESSELS DURING NEURAL ACTIVATION AND DEACTIVATION MEASURED BY TWO-PHOTON MICROSCOPY IN AWAKE MICE (2015)
  • Author(s): 田桑弘之
  • Organizer: XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function & XIIth International Conference
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2015-06-27
  • Int'l Joint Research
• [Presentation] 覚醒マウスを用いた脳血流動態および脳酸素代謝の光イメージングシステムの構築 (2014)
  • Author(s): 西野明日香
  • Organizer: 脳循環代謝学会
  • Place of Presentation: 岡山（岡山コンベンションセンター）
  • Year and Date: 2014-11-21
• [Presentation] 覚醒マウスの脳機能におけるマルチモダルイメージング (2014)
  • Author(s): 田桑 弘之
  • Organizer: 日本光学会
  • Place of Presentation: 東京（筑波大学）
  • Year and Date: 2014-11-05
  • Invited
• [Presentation] Newly optical imaging systems of change in oxygen metabolism and hemodynamic using awake mice brain (2014)
  • Author(s): 田桑 弘之
  • Organizer: 日本神経科学学会
  • Place of Presentation: 横浜（パシフィコ横浜）
  • Year and Date: 2014-09-12