Development of mouse model of neuromyelitis optica induced by aquaporin-4 protein immunization

• Project/Area Number: 22790375
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Chiba University
• Principal Investigator: UZAWA Akiyuki 千葉大学, 医学部・附属病院, 医員 (10533317)
• 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: 疾患モデル動物 / 視神経脊髄炎 / モデルマウス / 血液脳関門 / アクアポリン4 / インターロイキン6 / 接着因子

Research Abstract

To reveal the pathogenesis of neuromyelitis optica, we tried to develop mouse model of neuromyelitis optica induced by aquaporin-4 (AQP4) protein immunization. Although serum anti-AQP4 antibody titers were increased by the immunization with AQP4 protein, mice did not exhibit any symptoms and no inflammatory cell were observed in the central nervous system because of the presence of blood-brain barrier. When anti-AQP4 antibody was administered to the infant mice that were vulnerable BBB, inflammatory cells infiltrated in the periventricular spaces, leading that anti-AQP4 antibody itself may have pathogenicity.

Research Products

• [Journal Article] When is neuromyelitis optica diagnosed after disease onset? (2012)
  • Author(s): Uzawa A, Mori M, Muto M, Masuda S, Kuwabara S
  • Journal Title: J Neurol Volume: (in press) Issue: 8 Pages: 1600-5
  • DOI: 10.1007/s00415-011-6384-3
  • Peer Reviewed
• [Journal Article] Anti-N-methyl D-aspartate-type glutamate receptor antibody-positive limbic encephalitis in a patient with multiple sclerosis (2012)
  • Author(s): Uzawa A, Mori M, Takahashi Y, Ogawa Y, Uchiyama T, Kuwabara S
  • Journal Title: Clin Neurol Neurosurg Volume: (in press) Issue: 4 Pages: 402-404
  • DOI: 10.1016/j.clineuro.2011.10.047
  • Peer Reviewed
• [Journal Article] Seroconversion of anti-aquaporin-4 antibody in NMO spectrum disorder : a case report (2012)
  • Author(s): Mori M, Kawaguchi N, Uzawa A, Nemoto Y, Masuda S, Kuwabara S
  • Journal Title: J Neurol Volume: (in press) Issue: 5 Pages: 980-1
  • DOI: 10.1007/s00415-011-6288-2
  • Peer Reviewed
• [Journal Article] CSF interleukin-6 level predicts recovery from neuromyelitis optica relapse (2012)
  • Author(s): Uzawa A, Mori M, Sato Y, Masuda S, Kuwabara S
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 82 Issue: 3 Pages: 85-6
  • DOI: 10.1136/jnnp.2011.241760
  • Peer Reviewed
• [Journal Article] Markedly elevated sICAM-1 and sVCAM-1 levels in neuromyelitis optica : correlations with blood-brain barrier breakdown (2011)
  • Author(s): Uzawa A, Mori M, Masuda S, Kuwabara S
  • Journal Title: Arch Neurol Volume: 68 Issue: 7 Pages: 913-7
  • DOI: 10.1001/archneurol.2011.148
  • Peer Reviewed
• [Journal Article] Relapse of Neuromyelitis Optica Spectrum Disorder Associated with Intravenous Lidocaine (2011)
  • Author(s): Uzawa A, Mori M, Masuda S, Aoe K, Kuwabara S
  • Journal Title: Case Report Med Volume: 2011 Pages: 1-3
  • DOI: 10.1155/2011/405837
  • Peer Reviewed
• [Journal Article] Isolated abducens and facial nerve palsies due to a facial collicular plaque in multiple sclerosis (2011)
  • Author(s): Uzawa A, Mori M, Ito S, Kuwabara S
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 82 Issue: 1 Pages: 85-6
  • DOI: 10.1136/jnnp.2010.206870
  • Peer Reviewed
• [Journal Article] Detection of mumps virus RNA in cerebrospinal fluid of patients with neuromyelitis optica (2011)
  • Author(s): Mori M, Hosoya M, Hiwasa T, Hayakawa S, Uzawa A, Kuwabara S
  • Journal Title: Neurol Sci Volume: 32 Issue: 5 Pages: 795-9
  • DOI: 10.1007/s10072-011-0564-x
  • Peer Reviewed
• [Journal Article] 視神経脊髄炎と多発性硬化症の免疫病態の相違 (2011)
  • Author(s): 鵜沢顕之, 森雅裕, 桑原聡
  • Journal Title: 千葉医学会雑誌 Volume: 87 Pages: 291-4
  • NAID: 10030922443
  • Peer Reviewed
• [Journal Article] 視神経脊髄炎と多発性硬化症の免疫病態の相違 (2011)
  • Author(s): 鵜沢顕之
  • Journal Title: 千葉医学会雑誌 Volume: 87 Pages: 291-294
  • NAID: 10030922443
  • Peer Reviewed
• [Journal Article] CSF interleukin-6 level predicts recovery from neuromyelitis optica relapse (2011)
  • Author(s): Uzawa A, Mori M, et al
  • Journal Title: Journal of Neurology, Neurosurgery and Psychiatry Volume: (in press)
  • Peer Reviewed
• [Journal Article] Markedly elevated sICAM-1 and sVCAM-1 levels in neuromyelitis optica : correlations with blood-brain barrier breakdown (2011)
  • Author(s): Uzawa A, Mori M, et al
  • Journal Title: Archives of Neurology Volume: (in press)
  • Peer Reviewed
• [Journal Article] Cytokine and chemokine profiles in neuromyelitis optica : significance of interleukin-6 (2010)
  • Author(s): Uzawa A, Mori M, Arai K, Sato Y, Hayakawa S, Masuda S, Taniguchi J, Kuwabara S
  • Journal Title: Mult Scler Volume: 16 Issue: 12 Pages: 1443-52
  • DOI: 10.1177/1352458510379247
  • Peer Reviewed
• [Journal Article] Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica (2010)
  • Author(s): Uzawa A, Mori M, Hayakawa S, Masuda S, Nomura F, Kuwabara S
  • Journal Title: BMC Neurol Volume: 10 Issue: 1 Pages: 113-113
  • DOI: 10.1186/1471-2377-10-113
  • Peer Reviewed
• [Journal Article] Different responses to interferon beta-1b treatment in patients with neuromyelitis optica and multiple sclerosis (2010)
  • Author(s): Uzawa A, Mori M, Hayakawa S, Masuda S, Kuwabara S
  • Journal Title: Eur J Neurol Volume: 17 Issue: 5 Pages: 672-6
  • DOI: 10.1111/j.1468-1331.2009.02897.x
  • Peer Reviewed
• [Journal Article] Cytokine and chemokine profiles in neuromyelitis optica : significance of interleukin-6. (2010)
  • Author(s): Uzawa A, Mori M, et al.
  • Journal Title: Multiple Sclerosis Volume: 16 Pages: 1443-1452
  • Peer Reviewed
• [Presentation] Peptide array法によるAQP4上のimmunogenic site同定の試み (2012)
  • Author(s): 森雅裕, 鵜沢顕之, 増田冴子, 武藤真弓, 桑原聡
  • Organizer: 免疫性神経疾患に関する調査研究班班会議
  • Place of Presentation: 東京
• [Presentation] Cytokine Profiles in Neuromyelitis Optica : Significance of Interleukin-6 (2011)
  • Author(s): Akiyuki Uzawa
  • Organizer: Sendai NMO Conference
  • Place of Presentation: Sendai
  • Year and Date: 2011-07-16
• [Presentation] Cytokine Profiles in Neuromyelitis Optica : Significance of Interleukin-6 (2011)
  • Author(s): Akiyuki Uzawa
  • Organizer: Sendai NMO Conference
  • Place of Presentation: Sendai(招待講演)
  • Year and Date: 2011-07-16
• [Presentation] MSの経過中に抗GluR抗体陽性辺縁系脳炎を合併し、ステロイド治療が奏功した34歳女性例 (2011)
  • Author(s): 鵜沢顕之, 森雅裕, 内山智之, 小川喜胤, 桑原聡
  • Organizer: 日本神経治療学会
  • Place of Presentation: 福井
• [Presentation] MOでの可溶性ICAM-1、VCAM-1の上昇:血液脳関門破綻との関連 (2011)
  • Author(s): 鵜沢顕之, 森雅裕, 増田冴子, 桑原聡
  • Organizer: 日本神経免疫学会
  • Place of Presentation: 東京
• [Presentation] 免疫吸着療法による抗aquaporin-4抗体の除去能の検討 (2011)
  • Author(s): 森雅裕, 鵜沢顕之, 増田冴子, 武藤真弓
  • Organizer: 日本神経免疫学会
  • Place of Presentation: 東京
• [Presentation] 髄液サイトカインと視神経脊髄炎の予後に関する検討 (2011)
  • Author(s): 鵜沢顕之, 森雅裕, 増田冴子, 桑原聡
  • Organizer: 日本神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] ペプチドを用いた抗アクアポリン4抗体の抗原認識部位の探査 (2011)
  • Author(s): 森雅裕, 鵜沢顕之, 増田冴子, 桑原聡
  • Organizer: 日本神経学会総会
  • Place of Presentation: 名古屋
• [Presentation] 視神経脊髄炎のサイトカイン・ケモカインプロファイル (2011)
  • Author(s): 鵜沢顕之, 森雅裕, 桑原聡
  • Organizer: 免疫性神経疾患に関する調査研究班班会議
  • Place of Presentation: 東京
• [Presentation] NMOでの可溶性ICAM-1、VCAM-1の上昇:血液脳関門破綻との関連 (2011)
  • Author(s): 鵜沢顕之
  • Organizer: 日本神経免疫学会
  • Place of Presentation: 東京
• [Presentation] NMOとMSにおけるinterferonβ-1b治療反応性の差異に関する検討 (2010)
  • Author(s): 鵜沢顕之
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2010-05-22
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/neurol/kenkyu/achievement/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/neurol/kenkyu/achievement/index.html
• [Remarks]
  • URL: http://www.m.chiba-u.ac.jp/class/neurol/kenkyu/achievement/index.html