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

• Project/Area Number: 22791369
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Aichi 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: ¥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.

Research Products

• [Journal Article] Multifaceted neuro-regenerative activities of human dental pulp stem cells promote locomotor recovery after complete transection of the rat spinal cord (2012)
  • 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
  • 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 study (2011)
  • 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
• [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats (2011)
  • 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
• [Journal Article] Clinical Outcome of Treatment for Spinal Dural Arteriovenous Fistulas : the Results of Multivariate Analysis and Review of the Literatures (2011)
  • 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
• [Journal Article] Factors related to surgical outcome after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta (2011)
  • Author(s): Imagama S, Wakao N, Kitoh H, Matsuyama Y, Ishiguro N
  • Journal Title: Eur Spine J Jul Volume: 20
• [Journal Article] Differentiation of localization of spinal hemangioblastomas based on imaging and pathological findings (2011)
  • 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
• [Journal Article] Total En Bloc Spondylectomy for L2 Chordoma : A case report (2011)
  • 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)
• [Journal Article] Treatment for primary spinal atypical teratoid/rhabdoid tumor (2011)
  • 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)
• [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 investigation (2011)
  • 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)
• [Journal Article] A case of split notochord syndrome : an adult with a spinal endodermal cyst mimicking an intramedullary tumor (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Conservative treatment for cervical radiculopathy due to extensive foraminal disc calcification in children : a case report (2011)
  • Author(s): Imagama S, Wakao N, Ando K, Tauchi R, Tsuboi A, Ishiguro N
  • Journal Title: J Bone Joint Surg Am Volume: 93(16)
• [Journal Article] Clinical Outcome of Treatment for Spinal Dural Arteriovenous Fistulas : the Results of Multivariate Analysis and Review of the Literatures (2011)
  • 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
  • Peer Reviewed
• [Journal Article] Total En Bloc Spondylectomy for L2 Chordoma : A case report (2011)
  • Author(s): Norimitsu Wakao
  • Journal Title: Nagoya J Med Sci Volume: 73 Pages: 197-203
  • 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 study (2011)
  • Author(s): Imagama S, Wakao N, et al
  • Journal Title: Spine Volume: 36 Pages: 1204-1210
  • NAID: 10030715620
  • Peer Reviewed
• [Journal Article] Factors related to surgical outcome after posterior decompression and fusion for craniocervical junction lesions associated with osteogenesis imperfecta (2011)
  • Author(s): Imagama S, Wakao N, et al
  • Journal Title: Eur Spine J Volume: 20
  • Peer Reviewed
• [Journal Article] Differentiation of localization of spinal hemangioblastomas based on imaging (2011)
  • Author(s): Imagama S, Wakao N, et al
  • Journal Title: Eur Spine J Volume: 20 Pages: 1377-1384
  • Peer Reviewed
• [Journal Article] Treatment for primary spinal atypical teratoid/rhabdoid tumor (2011)
  • Author(s): Imagama S, Wakao N, et al
  • Journal Title: J Orthop Sci Volume: (In press)
  • 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 investigation (2011)
  • Author(s): Ando K, Wakao N, et al
  • Journal Title: J Neuros Spine Volume: 16 Pages: 147-153
  • Peer Reviewed
• [Journal Article] Conservative treatment for cervical radiculopathy due to extensive for aminal disc calcification in children : a case report (2011)
  • Author(s): Imagama S, Wakao N, et al
  • Journal Title: J Bone Joint Surg Am Volume: Aug 17:93 Pages: 15-15
  • Peer Reviewed
• [Journal Article] Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats (2011)
  • Author(s): Norimitsu Wakao
  • Journal Title: Neuroscience Letters Volume: 488 Pages: 299-304
  • Peer Reviewed
• [Journal Article] A case of split notochord syndrome : an adult with a spinal endodermalcyst mimicking an intramedullary tumor (2011)
  • Author(s): Norimitsu Wakao
  • Journal Title: Neuropathology Volume: (In Press 未定)
  • Peer Reviewed
• [Presentation] The management for Osteoporotic Vertebral Fracture in Japan (2011)
  • 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
• [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
• [Presentation] Preoperative paralysis negatively affects life prognosis following operative treatment for osteoporotic vertebral fracture (2011)
  • Author(s): Norimitsu Wakao
  • Organizer: 日本整形外科学会
  • Place of Presentation: (On line)
  • Year and Date: 2011-05-11
• [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
• [Presentation] The management for Osteoporotic Vertebral Fracture in Japan Invited Speaker Korean society for Osteoporosis (2011)
• [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
• [Presentation] Preoperative paralysis negatively affects life prognosis following operative treatment for osteoporotic vertebral fracture (2011)
  • Organizer: 日本整形外科学会総会(English session)
• [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
• [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
• [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
• [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
• [Presentation] 脊髄動静脈奇形の治療成績 (2010)
  • Organizer: 日本脊椎脊髄病学会
• [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
• [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
• [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