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Development of new therapies for vascular dementia

Research Project

Project/Area Number 22590958
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionKagawa University

Principal Investigator

UENO Masaki  香川大学, 医学部, 准教授 (30322267)

Co-Investigator(Kenkyū-buntansha) SAKAMOTO Haruhiko  香川大学, 医学部, 教授 (60106549)
黄 政龍  公益財団法人田附興風会, 医学研究所第一研究部, 研究主幹 (10271511)
小野寺 正征  香川大学, 医学部, 助教 (40359922)
Co-Investigator(Renkei-kenkyūsha) KOH Seiryu  公益財団法人田附興風会, 医学研究所第一研究部, 研究主幹
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords臨床神経形態学 / 血管性認知症 / オステオポンチン / CD36 / 血管脳関門 / Glut5 / 血液脳関門
Research Abstract

The expression of osteopontin, CD36, and LDL receptor (LDLR) was turned out to be increased in vessels showing blood-brain barrier (BBB) dysfunction. We could productsynthetic peptides of osteopontin, an antibody for osteopontin, virus vector expressing osteopontin. The expression of CD36 was turned out to be increased in the vessels showing BBB dysfunction in brains of hypertensive rats and senescence accelerated mice. Drugs inducing the reduction of CD36 or LDLR expression may be useful for the therapy against vascular dementia. In addition, angiotensin receptor blockers (ARBs) reduced vascular damage including the BBB damage, suggesting that the usage of ARBs with osteopontin may be effective for the therapy against vascular dementia.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (40 results)

All 2013 2012 2011 2010

All Journal Article (19 results) (of which Peer Reviewed: 19 results) Presentation (16 results) Book (5 results)

  • [Journal Article] CD36 expression in the brains of SAMP82013

    • Author(s)
      Wu B, Ueno M, Kusaka T, Miki T, Nagai Y, Nakagawa T, Kanenishi K, Hosomi N, Sakamoto H
    • Journal Title

      Archives of Gerontology and Geriatrics

      Volume: 56 Pages: 75-79

    • URL

      http://dx.doi.org/10.1016/j.archger.2012.07.007

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cerebral blood volume combined with amplitude-integrated EEG can be a suitable guide to control hypoxic/ischemic insult in a piglet model2013

    • Author(s)
      Shinji Nakamura
    • Journal Title

      Brain & Development

      Volume: 未定 Issue: 7 Pages: 614-625

    • DOI

      10.1016/j.braindev.2012.10.007

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The optimal timing of antihypertensive medication administration for morning hypertension in patients with cerebral infarction2012

    • Author(s)
      Hosomi N, Sueda Y, Masugata H, Dobashi H, Murao K, Ueno M, Miki T, Kohno M, Nishiyama A, Matsumoto M
    • Journal Title

      Hypertens Res

      Volume: 35 Issue: 7 Pages: 720-724

    • DOI

      10.1038/hr.2012.25

    • NAID

      10030956848

    • Related Report
      2012 Annual Research Report 2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] T-5224, a selective inhibitor of c-Fos/activator protein-1, attenuates lipopolysaccharide-induced liver injury in mice.2012

    • Author(s)
      Izuta S, Ueki M, Ueno M, Nishina K, Shiozawa S, Maekawa N. T-5224
    • Journal Title

      Biotech Lett

      Volume: 34 Issue: 12 Pages: 2175-2184

    • DOI

      10.1007/s10529-012-1022-4

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cerebral blood volume combined with amplitude-integrated EEG can be a suitable guide to control hypoxic/ischemic insult in a piglet model2012

    • Author(s)
      Nakamura S, Kusaka T, Yasuda S, Ueno M, Miki T, Koyano K, Nakamura M, Okada H, Okazaki K, Isobe K, Itoh S.
    • Journal Title

      Brain Dev

      Volume: (in press)

    • URL

      http://dx.doi.org/10.1016/j.braindev.2012.10.007

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Galectin-9 suppresses Th17 cell development in an IL-2-dependent but Tim-3-independent manner2012

    • Author(s)
      Oomizu S
    • Journal Title

      Clin Immunol

      Volume: 143(1) Issue: 1 Pages: 51-8

    • DOI

      10.1016/j.clim.2012.01.004

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cell surface galectin-9 expressing Th cells regulate Th17 and Foxp3+ Treg development by galectin-9 secretion.2012

    • Author(s)
      Oomizu S, Arikawa T, Niki T, Kadowaki T, Ueno M, Nishi N, Yamauchi A, Hattori T, Masaki T, Hirashima M.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 11 Pages: 1-10

    • DOI

      10.1371/journal.pone.0048574

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockage of AT1 receptors protects the blood-brain barrier and improve cognition in Dahl salt-sensitive hypertensive rats.2011

    • Author(s)
      Pelish N, Hosomi N, Ueno M, Nakano D, Hitomi H, Mogi M, Shimada K, Kobori H, Horiuchi M, Sakamoto H, Matsumoto M, Kohno M, Nishiyama A.
    • Journal Title

      Am J Hypertens

      Volume: 24 Issue: 3 Pages: 362-368

    • DOI

      10.1038/ajh.2010.241

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin II induces human astrocyte senescence through reactive oxygen species production2011

    • Author(s)
      Liu G, Hosomi N, Hitomi H, Pelish N, Fu H, Masugata H, Murao K, Ueno M, Matsumoto M, Nishiyama A.
    • Journal Title

      Hypertens Res

      Volume: 34 Issue: 4 Pages: 479-483

    • DOI

      10.1038/hr.2010.269

    • NAID

      10031163204

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The expression of CD36 in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model.2011

    • Author(s)
      Ueno M, Nakagawa T, Nagai Y, Nishi N, Kusaka T, Kanenishi K, Onodera M, Hosomi N, Huang C, Yokimise H, Tomimoto H, Sakamoto H.
    • Journal Title

      Neuropathology and Applied Neurobiology

      Volume: 37 Issue: 7 Pages: 727-737

    • DOI

      10.1111/j.1365-2990.2011.01172.x

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic effects of postischemic treatment with hypotensive doses of an angiotensin II receptor blocker on transient focal cerebral ischemia.2011

    • Author(s)
      Fu H, Hosomi N, Pelish N, Nakano D, Liu G, Ueno M, Miki T, Masagata H, Sueda Y, Itano T, Matsumoto M, Nishiyama A, Kohno M
    • Journal Title

      J Hypertens

      Volume: 29 Issue: 11 Pages: 2210-2219

    • DOI

      10.1097/hjh.0b013e32834bbb30

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet high-density lipoprotein activates transferring-derived phagocytosis activators, MAPPs, following thrombin digestion2011

    • Author(s)
      Sakamoto H, Wu B, Nagai Y, Tanaka S, Onodera M, Ogawa T, Ueno M
    • Journal Title

      Platelets

      Volume: 22 Issue: 5 Pages: 371-379

    • DOI

      10.3109/09537104.2010.533797

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Functional lateralization of sensorimotor cortex in infants measured using multichannel near-infrared spectroscopy2011

    • Author(s)
      Kusaka T
    • Journal Title

      Pediatric Research

      Volume: 69 Issue: 5 Part 1 Pages: 430-435

    • DOI

      10.1203/pdr.0b013e3182125cbd

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blockage of AT1 receptors protects the blood-brain barrier and improves cognition in Dahl salt-sensitive hypertensive rats.2011

    • Author(s)
      Pelisch N
    • Journal Title

      American Journal of Hypertension

      Volume: 24 Pages: 362-368

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The expression of LDL receptor in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model2010

    • Author(s)
      Ueno M, Wu B, Nakagawa T, Nagai Y, Onodera M, Huang C, Kusaka T, Kanenishi K, Sakamoto H
    • Journal Title

      Histochem Cell Biol

      Volume: 133 Issue: 6 Pages: 669-676

    • DOI

      10.1007/s00418-010-0705-y

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic canadesartan reduces brain angiotensin II via downregulation of brain-angiotensin system2010

    • Author(s)
      Pelisch N, Hosomi N, Ueno M, Masugata H, Murao K, Hitomi H, Nakano D, Kobori H, Nishiyama A, Kohno M.
    • Journal Title

      Hypertens Res

      Volume: 33 Issue: 2 Pages: 161-164

    • DOI

      10.1038/hr.2009.200

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] The expression of LDL receptor in vessels with blood-brain barrier impairment in a stroke-prone hypertensive model2010

    • Author(s)
      Ueno M
    • Journal Title

      Histochemistry and Cell Biology

      Volume: 133 Pages: 669-676

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transporters in the brain endothelial barrier2010

    • Author(s)
      Ueno M
    • Journal Title

      Current Medicinal Chemistry

      Volume: 17 Pages: 1125-1138

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Systemic candesartan reduces brain angiotensin II via downregulation of brain rennin-angiotensin system2010

    • Author(s)
      Pelisch N
    • Journal Title

      Hypertension Research

      Volume: 33 Pages: 161-164

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 酸化ストレスとアミロイドベータ蛋白輸送体の発現との関係について2012

    • Author(s)
      上野正樹、松本晃一、田中澄子、阪本晴彦
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Annual Research Report 2012 Final Research Report
  • [Presentation] 血液脳関門障害血管における CD36 の発現について2011

    • Author(s)
      上野正樹、松本晃一、阪本晴彦
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門障害血管における CD36 の発現について2011

    • Author(s)
      上野正樹、池田研二、阪本晴彦
    • Organizer
      第52回日本神経病理学会学術研究会
    • Place of Presentation
      京都
    • Related Report
      2012 Final Research Report
  • [Presentation] The mechanism of blood-brain barrier dysfunction in vascular dementia.2011

    • Author(s)
      Ueno M.
    • Organizer
      The 2ndCongress of Asian Society of Neuropathology.
    • Place of Presentation
      Beijing, China
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門障害血管における分子メカニズム解明から血管性認知症の治療へ2011

    • Author(s)
      上野正樹
    • Organizer
      第57回日本病理学会秋期特別総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門障害血管におけるCD36の発現について2011

    • Author(s)
      上野正樹
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜パシフィコ、横浜
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血液脳関門障害血管におけるCD36の発現について2011

    • Author(s)
      上野正樹
    • Organizer
      第52回日本神経病理学会総会学術研究会
    • Place of Presentation
      京都テルサ、京都
    • Related Report
      2011 Annual Research Report
  • [Presentation] 血液脳関門障害血管における分子メカニズム解明から血管性認知症の治療へ2011

    • Author(s)
      上野正樹
    • Organizer
      第57回日本病理学会秋期特別総会
    • Place of Presentation
      日本教育会館、東京(学術研究賞受賞演説)
    • Related Report
      2011 Annual Research Report
  • [Presentation] The mechanism of blood-brain barrier dysfunction in vascular dementia2011

    • Author(s)
      Masaki Ueno
    • Organizer
      The 2^<nd> Congress of Asian Society of Neuropathology
    • Place of Presentation
      北京中国科技会堂、Beijing, China(Symposium)
    • Related Report
      2011 Annual Research Report
  • [Presentation] Therapeutic targets for vascular dementia2010

    • Author(s)
      Ueno M, Onodera M, Sakamoto H
    • Organizer
      BIT's 1stannual world congress of NeuroTalk 2010
    • Place of Presentation
      Singapore
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門障害血管における LDL 受容体の発現について2010

    • Author(s)
      上野正樹、小野寺正征、松本晃一、阪本晴彦
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] 血液脳関門障害血管における LDL 受容体の発現について2010

    • Author(s)
      上野正樹、小野寺正征、阪本晴彦
    • Organizer
      第51回日本神経病理学会学術研究会
    • Place of Presentation
      東京
    • Related Report
      2012 Final Research Report
  • [Presentation] Gene analyses in vessels with blood-brain barrier impairment2010

    • Author(s)
      Ueno M, Onodera M, Sakamoto H
    • Organizer
      XVIIth International Congress of Neuropathology
    • Place of Presentation
      Salzburg, Austria
    • Related Report
      2012 Final Research Report 2010 Annual Research Report
  • [Presentation] Therapeutic targets for vascular dementia2010

    • Author(s)
      Ueno M
    • Organizer
      The BIT's 1^<st> Annual World Congress of NeuroTalk 2010
    • Place of Presentation
      Singapore EXPO, Singapore(招待講演)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血液脳関門障害血管におけるLDL受容体の発現について2010

    • Author(s)
      上野正樹
    • Organizer
      第99回日本病理学会総会
    • Place of Presentation
      京王プラザホテル(東京)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 血液脳関門障害血管におけるLDL受容体の発現について2010

    • Author(s)
      上野正樹
    • Organizer
      第51回日本神経病理学会総会学術研究会
    • Place of Presentation
      砂防会館別館(東京)
    • Related Report
      2010 Annual Research Report
  • [Book] Blood-brain barrier in SAMP82012

    • Author(s)
      Ueno M. Sakamoto H, Akiguchi I
    • Publisher
      Elesevier, The Senescence-Accelerated Mouse (SAM): Achievements and future directions
    • Related Report
      2012 Final Research Report
  • [Book] The Senescence-Accelerated Mouse (SAM)2012

    • Author(s)
      Masaki Ueno
    • Publisher
      Blood-brain barrier in SAMP8
    • Related Report
      2012 Annual Research Report
  • [Book] Transporters in the blood-brain barrier2011

    • Author(s)
      Ueno M, Nakagawa T, Sakamoto H.
    • Publisher
      Intech, Alzheimer's disease pathogenesis
    • Related Report
      2012 Final Research Report
  • [Book] Alzheimer's disease pathogenesis-core concepts, shifting paradigms and therapeutic targets2011

    • Author(s)
      Masaki Ueno
    • Publisher
      INTECH
    • Related Report
      2011 Annual Research Report
  • [Book] XVII International Congress of Neuropathology (Gene analyses in vessels with BBB impairment)2010

    • Author(s)
      Ueno M
    • Total Pages
      95
    • Publisher
      Medimomd
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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