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Molecular biology of GAG in the central nerve system and spinal cord injury.

Research Project

Project/Area Number 22791369
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionAichi Medical University (2011)
Nagoya University (2010)

Principal Investigator

WAKAO Norimitsu  愛知医科大学, 医学部, 助教 (80528802)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords脊髄損傷 / ヒアルロン酸オリゴ / 軸索伸長効果 / PKC,リン酸化PKC / 培養上清TNF-α, IL-1β、IL-6活性 / 急性期、亜急性期 / くも膜下、経口投与 / サル脊髄損傷モデル / 培養上清TNF-α,IL-1β、IL-6活性 / NMDA誘導神経細胞死 / PI calcein AM染色 / 培養上清LDH活性 / BDAトレーサー / Iba-1陽性領域 / ED-1陽性領域
Research Abstract

Hyaluronan is a component of the extracellular matrix of the central nervous system, and forms perineuronal nets around neurons. It has been recently reported that the hyaluronan-degrading enzyme hyaluronidase promotes lateral mobility of AMPA-type glutamate receptors and enhances synaptic plasticity. However, the biological significance of hyaluronan-degrading products(oligosaccharides) has not been studied in depth. Here we investigated the effects of hyaluronan oligosaccharides on motor function recovery after spinal cord injury in rats. The disaccharide HA2 and especially the tetrasaccharide HA4, significantly improved motor function, unlike the case with oligosaccharides composed of 6-12 saccharides. Consistent with this finding, HA4 treatment enhanced axonal regeneration/sprouting, as assessed by corticospinal tract tracer fiber counts. HA4 treatment also significantly suppressed accumulation of Iba-1-positive cells in a lesion two weeks after injury. In vitro experiments demonstrated that NMDA-induced neuronal cell death was partly blocked by HA4, but not by other oligosaccharides, whereas proteoglycan-mediated inhibition of neurite outgrowth was not affected by treatment with any oligosaccharide examined. Taken together, the present results revealed that due in part to its neuroprotective activity, HA4 promotes motor function recovery after spinal cord injury.

Report

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

    (36 results)

All 2012 2011 2010

All Journal Article (21 results) (of which Peer Reviewed: 12 results) Presentation (12 results) Book (3 results)

  • [Journal Article] Multifaceted neuro-regenerative activities of human dental pulp stem cells promote locomotor recovery after complete transection of the rat spinal cord2012

    • Author(s)
      Kiyoshi Sakai, Akihito Yamamoto#, Kohki Matsubara, Shoko Nakamura, Mami Naruse (#correspondence)
    • Journal Title

      The Journal of Clinical Investigation

      Volume: 122 Pages: 80-90

    • DOI

      10.1172/jci59251

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] An arterial pulse examination is not sufficient for diagnosis of peripheral arterial disease in lumbar spinal canal stenosis : a prospective multicenter study2011

    • Author(s)
      Imagama S, Matsuyama Y, Sakai Y, Ito Z, Wakao N, Deguchi M, Hachiya Y, Osawa Y, Yoshihara H, Kamiya M, Kanemura T, Kato F, Yukawa Y, Yoshida T, Harada A, Kawakami N, Suzuki K, Matsubara Y, Goto M, Sato K, Maruyama K, Yanase M, Ishida Y, Kuno N, Hasegawa T, Ishiguro N
    • Journal Title

      Spine(Phila Pa 1976)

    • NAID

      10030715620

    • Related Report
      2011 Final Research Report
  • [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats2011

    • Author(s)
      Wakao N, Imagama S, Zhang H, Tauchi R, Muramoto A, Natori T, Takeshita S, Ishiguro N, Matsuyama Y, Kadomatsu K
    • Journal Title

      Neurosci Lett

      Volume: 488 Pages: 299-304

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Journal Article] Clinical Outcome of Treatment for Spinal Dural Arteriovenous Fistulas : the Results of Multivariate Analysis and Review of the Literatures2011

    • Author(s)
      Wakao N, Imagama S, Ito Z, Ando K, Hirano K, Tauchi R, Muramoto A, Matsui H, Matsumoto T, Matsuyama Y, Ishiguro N
    • Journal Title

      SPINE

    • NAID

      10031169677

    • Related Report
      2011 Final Research Report
  • [Journal Article] Factors related to surgical outcome after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta2011

    • Author(s)
      Imagama S, Wakao N, Kitoh H, Matsuyama Y, Ishiguro N
    • Journal Title

      Eur Spine J Jul

      Volume: 20

    • Related Report
      2011 Final Research Report
  • [Journal Article] Differentiation of localization of spinal hemangioblastomas based on imaging and pathological findings2011

    • Author(s)
      Imagama S, Ito Z, Wakao N, Sakai Y, Kato F, Yukawa Y, Sato K, Ando K, Hirano K, Tauchi R, Muramoto A, Hashizume Y, Matsuyama Y, Ishiguro N
    • Journal Title

      Eur Spine J

    • Related Report
      2011 Final Research Report
  • [Journal Article] Total En Bloc Spondylectomy for L2 Chordoma : A case report2011

    • Author(s)
      Wakao N, Imagama S, Ito Z, Ando K, Hirano K, Tauchi R, Muramoto A, Matsui H, Matsumoto T, Matsuyama Y, Ishiguro N
    • Journal Title

      Nagoya J Med Sci

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Treatment for primary spinal atypical teratoid/rhabdoid tumor2011

    • Author(s)
      Imagama S, Wakao N, Ando K, Hirano K, Tauchi R, Muramoto A, Matsui H, Matsumoto T, Ukai J, Kobayashi K, Shinjo R, Nakashima H, Maruyama K, Matsuyama Y, Ishiguro N
    • Journal Title

      J Orthop Sci

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Examination of the influence of ossified anterior longitudinal ligament on symptom progression and surgical outcome of thoracic ossification of the ligamentum flavum : a multicenter study. Laboratory investigation2011

    • Author(s)
      Ando K, Imagama S, Wakao N, Ito Z, Hirano K, Tauchi R, Muramoto A, Matsuyama Y, Ishiguro N
    • Journal Title

      J Neuros Spine

      Volume: (in press)

    • Related Report
      2011 Final Research Report
  • [Journal Article] A case of split notochord syndrome : an adult with a spinal endodermal cyst mimicking an intramedullary tumor2011

    • Author(s)
      Norimitsu Wakao, Shiro Imagama(2番目), Yukihiro Matsuyama
    • Journal Title

      Neuropathology

      Volume: 31 Issue: 6 Pages: 626-31

    • DOI

      10.1111/j.1440-1789.2011.01212.x

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conservative treatment for cervical radiculopathy due to extensive foraminal disc calcification in children : a case report2011

    • Author(s)
      Imagama S, Wakao N, Ando K, Tauchi R, Tsuboi A, Ishiguro N
    • Journal Title

      J Bone Joint Surg Am

      Volume: 93(16)

    • Related Report
      2011 Final Research Report
  • [Journal Article] Clinical Outcome of Treatment for Spinal Dural Arteriovenous Fistulas : the Results of Multivariate Analysis and Review of the Literatures2011

    • Author(s)
      Norimitsu Wakao, Shiro Imagama(2番目), Yukihiro Matsuyama(10番目), 他7名
    • Journal Title

      Spine

      Volume: 15 Issue: 6 Pages: 482-488

    • DOI

      10.1097/brs.0b013e31822670df

    • NAID

      10031169677

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Total En Bloc Spondylectomy for L2 Chordoma : A case report2011

    • Author(s)
      Norimitsu Wakao
    • Journal Title

      Nagoya J Med Sci

      Volume: 73 Pages: 197-203

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An arterial pulse examination is not sufficient for diagnosis of peripheral arterial disease in lumbar spinal canal stenosis : a prospective multicenter study2011

    • Author(s)
      Imagama S, Wakao N, et al
    • Journal Title

      Spine

      Volume: 36 Pages: 1204-1210

    • NAID

      10030715620

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Factors related to surgical outcome after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta2011

    • Author(s)
      Imagama S, Wakao N, et al
    • Journal Title

      Eur Spine J

      Volume: 20

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differentiation of localization of spinal hemangioblastomas based on imaging2011

    • Author(s)
      Imagama S, Wakao N, et al
    • Journal Title

      Eur Spine J

      Volume: 20 Pages: 1377-1384

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment for primary spinal atypical teratoid/rhabdoid tumor2011

    • Author(s)
      Imagama S, Wakao N, et al
    • Journal Title

      J Orthop Sci

      Volume: (In press)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Examination of the influence of ossified anterior longitudinal ligament on symptom progression and surgical outcome of thoracic ossification of the ligamentum flavum : a multicenter study. Laboratory investigation2011

    • Author(s)
      Ando K, Wakao N, et al
    • Journal Title

      J Neuros Spine

      Volume: 16 Pages: 147-153

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conservative treatment for cervical radiculopathy due to extensive for aminal disc calcification in children : a case report2011

    • Author(s)
      Imagama S, Wakao N, et al
    • Journal Title

      J Bone Joint Surg Am

      Volume: Aug 17:93 Pages: 15-15

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats2011

    • Author(s)
      Norimitsu Wakao
    • Journal Title

      Neuroscience Letters

      Volume: 488 Pages: 299-304

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of split notochord syndrome : an adult with a spinal endodermalcyst mimicking an intramedullary tumor2011

    • Author(s)
      Norimitsu Wakao
    • Journal Title

      Neuropathology

      Volume: (In Press 未定)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] The management for Osteoporotic Vertebral Fracture in Japan2011

    • Author(s)
      Norimitsu Wakao
    • Organizer
      Korean society for Osteoporosis
    • Place of Presentation
      ソウル(招待講演)
    • Year and Date
      2011-12-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新ロコモティブシンドローム基準の検証2011

    • Author(s)
      若尾典充
    • Organizer
      日本整形外科学会
    • Place of Presentation
      (On line)
    • Year and Date
      2011-05-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] Preoperative paralysis negatively affects life prognosis following operative treatment for osteoporotic vertebral fracture2011

    • Author(s)
      Norimitsu Wakao
    • Organizer
      日本整形外科学会
    • Place of Presentation
      (On line)
    • Year and Date
      2011-05-11
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新ロコモティブシンドローム基準に腰椎疾患が及ぼす影響-腰痛関連指標、健康関連指標との比較検討-2011

    • Author(s)
      若尾典充
    • Organizer
      日本脊椎脊髄病学会
    • Place of Presentation
      (On line)
    • Year and Date
      2011-04-18
    • Related Report
      2011 Annual Research Report
  • [Presentation] The management for Osteoporotic Vertebral Fracture in Japan Invited Speaker Korean society for Osteoporosis2011

    • Related Report
      2011 Final Research Report
  • [Presentation] 新ロコモティブシンドローム基準の検証2011

    • Organizer
      日本整形外科学会総会
    • Related Report
      2011 Final Research Report
  • [Presentation] Preoperative paralysis negatively affects life prognosis following operative treatment for osteoporotic vertebral fracture2011

    • Organizer
      日本整形外科学会総会(English session)
    • Related Report
      2011 Final Research Report
  • [Presentation] 新ロコモティブシンドローム基準に腰椎疾患が及ぼす影響-腰痛関連指標、健康関連指標との比較検討-2011

    • Organizer
      日本脊椎脊髄病学会
    • Related Report
      2011 Final Research Report
  • [Presentation] 癌根治術における脊椎外科医の役割2011

    • Organizer
      Authentic Spinal Surgeon Summit
    • Place of Presentation
      Tokyo
    • Related Report
      2011 Final Research Report
  • [Presentation] 石灰化を伴う頸髄髄内病変主題2011

    • Organizer
      圧迫性脊髄症研究会
    • Related Report
      2011 Final Research Report
  • [Presentation] 脊髄動静脈奇形の症状と診断に関する検討2010

    • Organizer
      日本脊椎脊髄病学会
    • Related Report
      2011 Final Research Report
  • [Presentation] 脊髄動静脈奇形の治療成績2010

    • Organizer
      日本脊椎脊髄病学会
    • Related Report
      2011 Final Research Report
  • [Book] 脊髄病変髄内腫瘍2011

    • Author(s)
      若尾典充
    • Total Pages
      10
    • Publisher
      金原出版社
    • Related Report
      2011 Annual Research Report
  • [Book] 【脊髄・馬尾腫瘍の手術安全な腫瘍摘出のために】馬尾腫瘍手術intraoperative nerve root stimulationの活用(解説/特集)2011

    • Author(s)
      若尾典充
    • Total Pages
      10
    • Publisher
      整形・災害外科(0387-4095)53巻11号Page1289-1298
    • Related Report
      2011 Annual Research Report
  • [Book] 脊椎・脊髄画像診断脊髄病変髄内腫瘍2010

    • Author(s)
      若尾典充、今釜史郎, 安藤圭, 平野健一, 田内亮吏, 村本明生, 松井寛樹, 石黒直樹, 松山幸弘
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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