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2007 Fiscal Year Final Research Report Summary

Pathogenesis of ischemic white matter lesions ; an analysis using a novel mouse model for vascular dementia.

Research Project

Project/Area Number 18590936
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTazuke Kofukai Medical Research Institute

Principal Investigator

SAIKI Hidemoto  Tazuke Kofukai Medical Research Institute, 4 Division, Medical Research Institute, Researcher (90378688)

Co-Investigator(Kenkyū-buntansha) TOMIMOTO Hidekazu  Kyoto University, Graduate School of Medicine, Lecturer (80324648)
Project Period (FY) 2006 – 2007
Keywordswhite matter lesions / chronic cerebral hypoperfusion / blood-brain barrier / knockout mouse / basement membrane / extracellular matrix / subcortical vascular dementia / matrix metalloproteinase(MMP)
Research Abstract

White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, we examined the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence of MMP-2-expressing activated microglia in the optic tract and corpus callosum, most numerously on day 3. In contrast, the capillary endothelial cells expressed MMP-2 later.
IgM-immunoreactive glial cells were absent in the sham operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood-brain barrier. These findings suggest that the main sources of the elevated MMP-2 were the microglia and the endothelium, and that these cells may contribute to the remodeling of the white matter myelin and microvascular beds in chronic cerebral hypoperfusion.

  • Research Products

    (10 results)

All 2007 2006

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (2 results)

  • [Journal Article] Capillary beds are decreased in Alzheimer's disease, but not in Binswanger's disease.2007

    • Author(s)
      Kitaguchi H,Ihara M,Saiki H,Takahashi R and Tomimoto H
    • Journal Title

      Neurosci Lett 417

      Pages: 128-131

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion2007

    • Author(s)
      Ohtani R,Tomimoto H,Wakita H,Kitaguchi H,Nakaji K,Takahashi R
    • Journal Title

      Brain Research 1135

      Pages: 195-200

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion.2007

    • Author(s)
      Shibata M,Yamasaki N,Miyakawa T,Ohta ni R,Ihara M,Takahashi R,Tomimoto H
    • Journal Title

      Stroke 38

      Pages: 2826-2832

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Capillary beds are decreased in Alzheimer's disease, but not in Binswanger's disease.2007

    • Author(s)
      Kitaguchi H, Ihara M, Saiki H, Takahashi R, Tomimoto H.
    • Journal Title

      Neurosci Lett 417

      Pages: 128-131

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expression of S100 protein and protective effect of arundic acid on the rat brain in chronic cerebral hypoperfusion.2007

    • Author(s)
      Ohtani R, Tomimoto H, Wakita H, Kitaguchi H, Nakaji K, Takahashi R.
    • Journal Title

      Brain Research 1135

      Pages: 195-200

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Selective impairment of working memory in a mouse model of chronic cerebral hypoperfusion.2007

    • Author(s)
      Shibata M, Yamasaki N, Miyakawa T, Ohta ni R, Ihara M, Takahashi R, Tomimoto H
    • Journal Title

      Stroke 38

      Pages: 195-200

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] MMP-2 play a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents.2006

    • Author(s)
      Nakaji K,Ihara M,Takahashi C,Itohara S,Noda N,Takahashi R and Tomimoto H
    • Journal Title

      Stroke 37

      Pages: 2816-2823

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] MMP-2 play a critical rolde in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents.2006

    • Author(s)
      Nakaji K, Ihara M, Takahashi C, Itohara S, Noda N, Takahashi R, Tomimoto H.
    • Journal Title

      Stroke 37

      Pages: 2816-2823

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] アルツハイマー病におけるcapillary networkの障害;Silver impregnation techniqueによる剖検脳の検討。2006

    • Author(s)
      北口浩史、猪原匡史、高橋良輔、冨本秀和
    • Organizer
      第47回日本神経学会総会
    • Place of Presentation
      東京
    • Year and Date
      2006-05-23
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Capillary network is impaired in Alzheimer's disease ; an analysis of autopsied brains using silver impregnation method.2006

    • Author(s)
      Kitaguchi H, Ihara M, Takahashi R, Tomimoto H.
    • Organizer
      47th annual meeting of Japanse Neurological Association
    • Year and Date
      2006-05-23
    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2010-02-04  

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