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Newly synthesized radical-containing nanoparticles (RNP) enhance neuroprotection after cerebral ischemia-reperfusion injury

Research Project

Project/Area Number 23592085
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cerebral neurosurgery
Research InstitutionUniversity of Tsukuba

Principal Investigator

TSURUSHIMA Hideo  筑波大学, 医学医療系, 准教授 (50315470)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywordsdrug delivery system / ナノ粒子 / 脳梗塞 / 活性酸素消去 / 治療 / ナノメディスン / 脳虚血 / DDS / 血管新生
Research Abstract

Antioxidant nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) have been investigated for their ability to scavenge free radicals produced by ischemia-reperfusion injury. However, the short in vivo half-life and toxicity of TEMPO was reported. We developed a core-shell-type nanoparticle, termed a radical-containing nanoparticle (RNP). We evaluated the ability of RNP to deliver TEMPO radicals to the ischemic brain and scavenge free radicals in cerebral ischemia-reperfusion injury. RNPs were detected for 6 h after intravenous administration in the ischemic brain, and significantly reduced the production of superoxide anion in neuronal cells. The infarction volumes of rats treated by RNPs were significantly lower than those of rats treated by saline, micelles, and TEMPOL. RNP treatment suppressed lipid peroxidation and protein oxidation, and limited the adverse effects of TEMPO radicals such as hypotension. RNPs could be a promising neuroprotective agent.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (39 results)

All 2014 2013 2012 2011 Other

All Journal Article (27 results) (of which Peer Reviewed: 27 results) Presentation (7 results) Book (3 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Coprecipitation of DNA-lipid complexes with apatite and comparison with superficial adsorption for gene transfer applications.2014

    • Author(s)
      Yazaki Y, Oyane A, Tsurushima H, Araki H, Sogo Y, Ito A, Yamazaki A,
    • Journal Title

      J Biomater Appli

      Volume: 28 Pages: 937-945

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneous assembly of DNA-amorphous calcium phosphate nanocomposite spheres for surface-mediated genetransfer2013

    • Author(s)
      Oyane A, Tsurushima H
    • Journal Title

      Cryst Eng Comm

      Volume: 15(25) Pages: 4994-4997

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Size-dependent radiosensitization effects of gold nanoparticles on human U251 malignant glioma cells2013

    • Author(s)
      Zaboronok A, Tsurushima H
    • Journal Title

      Nanosci Nanotech Lett

      Volume: 5 Pages: 990-994

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis therapy for brain infarction using a slow-releasing drug delivery system for fibroblast growth factor 22013

    • Author(s)
      Ito Y, Tsurushima H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 432(1) Pages: 182-187

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors of ischemic lesions related to cerebral angiography and neuro-interventional procedures2013

    • Author(s)
      Sato M, Tsurushima H
    • Journal Title

      Neurol Med Chir (Tokyo)

      Volume: 53(6) Pages: 381-387

    • NAID

      10031173721

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA-lipid-apatitie composite layers enhance gene expression of mesenchymal stem cells2013

    • Author(s)
      Wang X, Tsurushima H
    • Journal Title

      Mat Sci Eng C

      Volume: 30 Pages: 512-518

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA-lipid-apatitie composite layers enhance gene expression of mesenchymal stem cells.2013

    • Author(s)
      Wang X, Ito A, Sogo Y, Hirose M, Oyane A, Tsurushima H,
    • Journal Title

      Mat Sci Eng C

      Volume: 33 Pages: 512-518

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Risk factors of ischemic lesions related to cerebral angiography and neuro-interventional procedures.2013

    • Author(s)
      Sato M, Nakai Y, Tsurushima H , Shiigai M, Masumoto T, Matsumura A,
    • Journal Title

      Neurol Med Chir (Tokyo)

      Volume: 53 Pages: 381-387

    • NAID

      10031173721

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis therapy for brain infarction using a slow-releasing drug delivery system for fibroblast growth factor 2.2013

    • Author(s)
      Ito Y, Tsurushima H, Sato M, Ito A, Oyane A, Sogo Y, Matsumura A,
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 432 Pages: 182-187

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain metastasis from papillary thyroid carcinomas.2013

    • Author(s)
      Tsuda K, Tsurushima H, Takano S, Tsuboi K, Matsumura A,
    • Journal Title

      Mol Clin Onc

      Volume: 1 Pages: 817-819

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Size-dependent radiosensitization effects of gold nanoparticles on human U251 malignant glioma cells.2013

    • Author(s)
      Zaboronok A, Tsurushima H, Yamamoto T, Isobe T, Takada K, Sakae T, Yoshida F, Matsumura A,
    • Journal Title

      Nanosci Nanotech Lett

      Volume: 5 Pages: 990-994

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Spontaneous assembly of DNA-amorphous calcium phosphate nanocomposite spheres for surface-mediated genetransfer.2013

    • Author(s)
      Oyane A, Araki H, Sogo Y, Ito A, Tsurushima H,
    • Journal Title

      Cryst Eng Comm

      Volume: 15 Pages: 4994-4997

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Calcium phosphate coating on a bioresorbable hudroxyapatite/collagen nanocomposite for surface functionalization.2013

    • Author(s)
      Bodhak S, Kikuchi M, Sogo Y, Tsurushima H, Ito A, Oyane A,
    • Journal Title

      Chem Lett

      Volume: 42 Pages: 1029-1031

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiogenesis therapy for brain infarction using a slow-releasing drug delivery system for fibroblast growth factor 2.2013

    • Author(s)
      Ito Y, Tsurushima H, Sato M, Ito A, Oyane A, Sogo Y, Matsumura A
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 432(1) Pages: 182-187

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Fabrication of DNA-antibody-apatitie composite layers for cell-targeted gene transfer2012

    • Author(s)
      Yazaki Y, Tsurushima H
    • Journal Title

      Sci Technol Adv Mater

      Volume: 13 Pages: 8-8

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fabrication of a DNA–lipid–apatite composite layer for efficient and area-specific gene transfer2012

    • Author(s)
      Oyane A, Tsurushima H
    • Journal Title

      J Mater Sci Mater Med

      Volume: 23(4) Pages: 1011-1019

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A subpopulation of endothelial progenitor cells with low aldehyde dehydrogenase activity attenuates acute ischemic brain injury in rats2012

    • Author(s)
      Nakamura K, Tsurushima H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 418(1) Pages: 87-92

    • NAID

      120007130720

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cilostszol suppression of arterial intimal hyperplasia is associated with decreased expression of sialyl Lewis X homing receptors on mononuclear cells and E-selectin in endothelial cells2012

    • Author(s)
      Takigawa T, Tsurushima H
    • Journal Title

      J Vascular Surgery

      Volume: 55(2) Pages: 506-516

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] BMP-2 gene-fibronectin-apatitie composite layer enhances bone formation2011

    • Author(s)
      Zhang W, Tsurushima H
    • Journal Title

      J Biomed Sci

      Volume: 18 Pages: 62-62

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] BMP-2 and ALP gene expression induced by BMP-2gene-fibronectin-apatite composite layer2011

    • Author(s)
      X.P. Wang, A. Oyane, H. Tsurushima, Y. Sogo, X. Li, and A. Ito
    • Journal Title

      Biomed. Mater.

      Volume: 6 Issue: 4 Pages: 45004-45009

    • DOI

      10.1088/1748-6041/6/4/045004

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Control of gene transfer on a DNA-fibronectin-apatite composite layer by the incorporation of carbonate and fluoride ions2011

    • Author(s)
      Yazaki Y, Tsurushima H
    • Journal Title

      Biomaterials

      Volume: 32 Pages: 4896-4902

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Osteoblast differentiation and disinfection induced by nitrogen plasma-treated surfaces2011

    • Author(s)
      Zhang W, Tsurushima H
    • Journal Title

      Biomed Mater Eng

      Volume: 21(2) Pages: 75-82

    • NAID

      120007137460

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Time-course analysis of brain perfusion single-photon emission computed tomography using a three-dimentional stereotactic region-of-interest template in patients with Moyamoya disease2011

    • Author(s)
      Marushima A, Tsurushima H
    • Journal Title

      World Neurosurg

      Volume: 76(3-4) Pages: 304-310

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Newly synthesized radical-containing nanoparticles (RNP) enhance neuroprotection after cerebral ischemia-reperfusion injury2011

    • Author(s)
      Marushima A, Tsurushima H
    • Journal Title

      Neurosurgery

      Volume: 68(5) Pages: 1418-1426

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Newly synthesized radical-containing nanoparticles (RNP) enhance neuroprotection after cerebral ischemia-reperfusion injury.2011

    • Author(s)
      Marushima A, Suzuki K, Nagasaki Y, Yoshitomi T, Toh K, Tsurushima H (CA), Hirayama A, Matsumura A
    • Journal Title

      Neurosurgery

      Volume: 68 Pages: 1418-1426

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Control of gene transfer on a DNA-fibronectin-apatite composite layer by the incorporation of carbonate and fluoride ions.2011

    • Author(s)
      Yazaki Y, Oyane A, Sogo Y, Ito A, Yamazaki A,Tsurushima H (CA),
    • Journal Title

      Biomaterials

      Volume: 32 Pages: 4896-4902

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] BMP-2 gene-fibronectin-apatitie composite layer enhances bone formation.2011

    • Author(s)
      Zhang W, Tsurushima H (CA), Oyane A, Yazaki Y, Sogo Y, Ito A, Matsumura A,
    • Journal Title

      J Biomed Sci

      Volume: 18 Pages: 62-62

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/21859498

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] 血管内皮前駆細胞を用いた脳虚血治療に関する基礎的検討2013

    • Author(s)
      鶴嶋英夫(代表)
    • Organizer
      第72回日本脳神経外科学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 血管内皮前駆細胞を用いた脳虚血治療に関する基礎的検討、2013

    • Author(s)
      鶴嶋英夫、佐藤允之、中村和弘、丸島愛樹、伊藤嘉朗、長野真澄、山下年晴、大根田修、松村明、
    • Organizer
      第72回日本脳神経外科学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脳組織保護作用、血管・骨再生作用をもたらすFGF-2徐放性Drug Delivery System2012

    • Author(s)
      鶴嶋英夫(代表)
    • Organizer
      第71回日本脳神経外科学術総会
    • Place of Presentation
      大阪
    • Year and Date
      2012-10-17
    • Related Report
      2013 Final Research Report
  • [Presentation] FGF-2徐放ドラッグデリバリーシステムによる脳血管新生療法2012

    • Author(s)
      伊藤嘉朗、鶴嶋英夫、佐藤允之、伊藤敦夫、大矢根綾子、十河友、松村明
    • Organizer
      Stroke2012
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] 虚血性脳血管障害におけるDrug Delivery Systemナノ粒子治療—ナノ粒子の臨床応用の可能性−2011

    • Author(s)
      鶴嶋英夫(代表)
    • Organizer
      第70回日本能神経外科学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 虚血性脳血管障害におけるDrug Delivery Systemナノ粒子治療2011

    • Author(s)
      鶴嶋英夫(代表)
    • Organizer
      第70回日本脳神経外科学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] 虚血性脳血管障害におけるDrug Delivery Systemナノ粒子治療 (シンポジウム)2011

    • Author(s)
      鶴嶋英夫、鶴田和太郎、丸島愛樹、伊藤嘉朗、中村和弘、松村明
    • Organizer
      第70回日本脳神経外科学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2011 Research-status Report
  • [Book] やさしい臨床医学テキスト2014

    • Author(s)
      鶴嶋英夫
    • Total Pages
      506
    • Publisher
      薬事日報社
    • Related Report
      2013 Annual Research Report
  • [Book] Springer Malignant Brain Tumors, Tumors of the Central Nervous system 2011 vol.32011

    • Author(s)
      Tsurushima H
    • Total Pages
      382
    • Publisher
      Role of Radioresponsive Gene Therapy
    • Related Report
      2013 Final Research Report
  • [Book] Tumors of the Central Nervous system, Volume 32011

    • Author(s)
      Tsurushima H, Matsumura A,
    • Publisher
      Springer
    • Related Report
      2011 Research-status Report
  • [Remarks] ・2011年 ABC Award, ABC2011受賞, (Antibody immobilized in a DNA・・・)・2011年 ABC Award, ABC2011受賞, (Influence of Ca2+ and Mg2+・・・) (上記2つとも

    • URL

      http://www.ceramic.or.jp/bseitai/ABC2011/index.html)

    • Related Report
      2011 Research-status Report
  • [Patent(Industrial Property Rights)] 生体内留置物可視化装置2011

    • Inventor(s)
      鶴嶋英夫など
    • Industrial Property Rights Holder
      筑波大学、産業技術総合研究所、高エネルギー研究機構
    • Filing Date
      2011
    • Related Report
      2011 Research-status Report

URL: 

Published: 2011-08-05   Modified: 2019-07-29  

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