Neuranagenesis factor and comprehensive gene analysis for spinal cord injury

• Project/Area Number: 22390287
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: University of Fukui
• Principal Investigator: BABA Hisatoshi 福井大学, 医学部, 教授 (00165060)
• Co-Investigator(Kenkyū-buntansha): UCHIDA Kenzo 福井大学, 医学部, 准教授 (60273009)
• Co-Investigator(Renkei-kenkyūsha): FURUKAWA Shoei 岐阜薬科大学, 薬学部, 教授 (90159129)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2010: ¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
• Keywords: 脊椎脊髄病学 / 脊髄神経再生 / 脊髄損傷 / 軸索再生 / 脊髄再生 / 網羅的遺伝子解析 / siRNA / 慢性脊髄圧迫 / マイクロアレイ / 遺伝子解析 / 神経再生因子 / メカニカルストレス

Research Abstract

The present study was designed to investigate the effect of cyclic tensile stresses on cultured spinal cord cells using the Flexercell Strain Unit and DNA microarray technology.Spinal cord cells were isolated for culture from 15-day Sprague-Dawley rat embryos. The application of cyclic tensile stress reduced the viability of cultured spinal cord cells significantly in a dose- and time-dependent manner. Increasing either the strain or the strain rate independently was associated with significant decreases in spinal cord cell survival. There was no clear evidence of additive effects of strain level with strain rate. GO analysis identified 44 candidate genes which were significantly related to “apoptosis” and 17 genes related to “response to stimulus”. KEGG analysis identified changes in the expression levels of 12 genes of the mitogen-activated protein kinase (MAPK) signaling pathway, which were confirmed to be upregulated by RT-PCR analysis. These data may prove useful, as the accurate knowledge of neuronal gene expression in response to cyclic tensile stress will help in the development of molecular-based therapies for spinal cord injury.

Research Products

• [Journal Article] Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice (2012)
  • Author(s): Guerrero AR, Uchida K, Nakajima H, Watanabe S, Nakamura M, Johnson WE, Baba H
  • Journal Title: J Neuroinflammation Volume: 27:9:40
  • Peer Reviewed
• [Journal Article] Transplantation of mesenchymal stem cells promotes an alternative pathway of macrophage activation and functional recovery after spinal cord injury (2012)
  • Author(s): Nakajima H, Uchida K, Guerrero AR, Watanabe S, Sugita D, Takeura N, Yoshida A, Long G, Wright KT, Johnson WE, Baba H
  • Journal Title: J Neurotrauma Volume: 29 Pages: 1614-1625
  • Peer Reviewed
• [Journal Article] The retrograde delivery of adenovirus vector carrying the gene for brain-derived neurotrophic factor protects neurons and oligodendrocytes from apoptosis in the chronically compressed spinal cord of twy/twy mice (2012)
  • Author(s): Uchida K
  • Journal Title: Spine Volume: 37 Pages: 2125-2135
  • NAID: 10031169894
  • Peer Reviewed
• [Journal Article] Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice (2012)
  • Author(s): Guerrero AR
  • Journal Title: J Neuroinflammation Volume: 27 Pages: 40-40
  • Peer Reviewed
• [Journal Article] High-mobility Group Box-1 and Its Receptors Contribute to Proinflammatory Response in the Acute Phase of Spinal Cord Injury in Rats (2011)
  • Author(s): Chen KB, Uchida K, Nakajima H, Yayama T, Hirai T, Guerrero AR, Kobayashi S, Ma WY, Liu SY, Zhu P, Baba H
  • Journal Title: Spine Volume: 36 Pages: 2122-2129
  • NAID: 10030901954
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-alpha antagonist reduces apoptosis of neurons and oligodendroglia in rat spinal cord injury (2011)
  • Author(s): Chen KB, Uchida K, Nakajima H, Yayama T, Guerrero AR, Kobayashi S, Ma WY, Liu SY, Baba H
  • Journal Title: Spine Volume: 36 Pages: 1350-1358
  • Peer Reviewed
• [Journal Article] High-mobility group boX-1 and its receptors contribute to proinflammatory response in the acute phase of spinal cord injury in rats (2011)
  • Author(s): Chen KB, Uchida K, Nakajima H, Yayama T, Hirai T, Rodriguez Guerrero A, Kobayashi S, Ma WY, Liu SY, Zhu P, Baba H
  • Journal Title: Spine (Phila Pa 1976) Volume: 36 Pages: 2122-2129
  • NAID: 10030901954
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-α antagonist reduces apoptosis of neurons and oligodendroglia in rat spinal cord injury (2011)
  • Author(s): Chen KB, Uchida K, Nakajima H, Yayama T, Hirai T, Watanabe S, Guerrero AR, Kobayashi S, Ma WY, Liu SY, Baba H
  • Journal Title: Spine (Phila Pa 1976) Volume: 36 Pages: 1350-1358
  • NAID: 10030716262
  • Peer Reviewed
• [Journal Article] Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro (2010)
  • Author(s): Uchida K, Nakajima H, Hirai T, Yayama T, Chen KB, Kobayashi S, Roberts S, Johnson WE, Baba H.
  • Journal Title: BMC Neurosci Volume: 11 Pages: 84-84
  • Peer Reviewed
• [Journal Article] Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats (2010)
  • Author(s): Nakajima H, Uchida K, Yayama T, Kobayashi S, Guerrero AR, Furukawa S, Baba H
  • Journal Title: Spine Volume: 35 Pages: 497-504
  • NAID: 10028062172
  • Peer Reviewed
• [Journal Article] Microarray analysis of expression of cell death-associated genes in rat spinal cord cells exposed to cyclic tensile stresses in vitro. (2010)
  • Author(s): Uchida K, Nakajima H, Hirai T, Yayama T, Chen KB, Kobayashi S, Roberts S, Johnson WE, Baba H
  • Journal Title: BMC Neurosci Volume: 11 Pages: 84-84
  • Peer Reviewed
• [Journal Article] Targeted retrograde gene delivery of brain-derived neurotrophic factor suppresses apoptosis of neurons and oligodendroglia after spinal cord injury in rats. (2010)
  • Author(s): Nakajima H, Uchida K, Yayama T, Kobayashi S, Guerrero AR, Furukawa S, Baba H.
  • Journal Title: Spine Volume: 35 Pages: 497-504
  • NAID: 10028062172
  • Peer Reviewed
• [Journal Article] 脊髄再生基礎科学の現状と近未来の展望、Myelopathyに対するアデノウィルスベクターを用いた逆行性神経栄養因子遺伝子療法による脊髄保護効果 (2010)
  • Author(s): 内田研造、中嶋秀明、渡邉修司、馬場久敏
  • Journal Title: 脊椎脊髄ジャーナル Volume: 23 Pages: 859-866
• [Journal Article] Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice
  • Author(s): Guerrero AR, Uchida K, Nakajima H, Watanabe S, Nakamura M, Johnson WE, Baba H
  • Journal Title: J Neuroinflammation Volume: (in press)
  • Peer Reviewed
• [Journal Article] Transplantation of Mesenchymal Stem Cells Promotes the Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury
  • Author(s): Nakajima H, Uchida K, Rodriguez Guerrero A, Watanabe s, Sugita D, Takeura N, Yoshida A, Long G, Wright K, Johnson E, Baba H
  • Journal Title: J Neurotrauma Volume: (in press)
  • Peer Reviewed
• [Journal Article] Tumor necrosis factor-alpha antagonist reduces apoptosis of neurons and oligodendroglia in rat spinal cord injury.
  • Author(s): Chen KB, Uchida K, Nakajima H, Yayama T, Guerrero AR, Kobayashi S, Ma WY, Liu SY, Baba H.
  • Journal Title: Spine Volume: (in press)
  • Peer Reviewed
• [Journal Article] High-mobility group box-1 and its receptors contribute to proinflammatory response in the acute phase of spinal cord injury in rats.
  • Author(s): Uchida K, Nakajima H, Yayama T, Hirai T, Guerrero AR, Koba yashi S, Ma WY, Liu SY, Zhu P, Baba H．
  • Journal Title: Spine Volume: (in press)
  • NAID: 10030901954
  • Peer Reviewed
• [Presentation] Blockade of interleukin-6 signaling improves the survival rate of transplanted bone marrow stromal cells after spinal cord injury (2012)
  • Author(s): Nakajima H
  • Organizer: 40th Annual Meeting of the Cervical Spine Research Society
  • Place of Presentation: Chicago, USA
• [Presentation] マウス脊髄損傷モデルを用いた骨髄間質細胞移植後のMAPK シグナル伝達経路に関する免疫組織学的検討 (2012)
  • Author(s): 渡邉修司
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
• [Presentation] 脊髄運動ニューロンに対するヒト骨髄間質細胞の軸索伸展メカニズム (2012)
  • Author(s): 内田研造
  • Organizer: 第27回日本整形外科学会基礎学術集会
  • Place of Presentation: 名古屋
• [Presentation] 慢性脊髄圧迫モデル（twy/twy)を用いた骨髄由来マクロファージの極性変化に関する組織学的検討 (2012)
  • Author(s): 平井貴之
  • Organizer: 第41回日本脊椎脊髄病学会
  • Place of Presentation: 久留米
• [Presentation] Blockade of interleukin-6 signaling generates an alternative activating environment in the spinal cord after injury:Promoting a neuroprotective macrophage population with concurrent locomotive recovery in mice (2011)
  • Author(s): Guerrero AR, Uchida K, Nakajima H, Hirai T, Watanabe S, Baba H
  • Organizer: 39th Annual Meeting of The Cervical Spine Research Society(CSRS 2011)
  • Place of Presentation: Arizona(USA)
  • Year and Date: 2011-12-08
• [Presentation] Blockade of interleukin-6 signaling generates an alternative activating environment in the spinal cord after injury : Promoting a neuroprotective macrophage population with concurrent locomotive recovery in mice (2011)
  • Author(s): Alexander Guerrero, K. Uchida, H.Nakajima, T.Hirai, S.Watanabe, H.Baba
  • Organizer: 39th Annual Meeting of The Cervical Spine Research Society (CSRS 2011)
  • Place of Presentation: Arizona(USA)
  • Year and Date: 2011-12-08
• [Presentation] Microarray analysis of cell death-associated genes in rat embryo cultured spinal cord cells exposed to cyclic tensile stresses in vitro (2011)
  • Author(s): Uchida K, Nakajima H, Hirai T, Watanabe S, Guerrero AR, Baba H.
  • Organizer: The 27th Annual Meeting of the CSRS-ES
  • Place of Presentation: Istanbul(Turkey)
  • Year and Date: 2011-06-08
• [Presentation] メカニカルストレスに対する培養脊髄ニューロンの MAPK キナーゼに関する遺伝子発現プロファイル (2011)
  • Author(s): 内田研造, 中嶋秀明, 彌山峰史, 杉田大輔, 渡邉修司, 馬場久敏
  • Organizer: 第84回日本整形外科学会学術総会
  • Place of Presentation: Web 開催
  • Year and Date: 2011-05-12
• [Presentation] メカニカルストレスに対する培養脊髄ニューロンのMAPKキナーゼに関する遺伝子発現プロファイル (2011)
  • Author(s): 内田研造, 中嶋秀明, 彌山峰史, 杉田大輔, 渡邉修司, 馬場久敏
  • Organizer: 第84回日本整形外科学会学術総会
  • Place of Presentation: (Web開催)
  • Year and Date: 2011-05-12
• [Presentation] Some neuroprotective mathods for spinal cord injury (2011)
  • Author(s): Baba H, Uchida K, Nakajima H, WatanabeS, Takeura N, Yayama T
  • Organizer: The 13rd Intedrnational Southern China Cardiology Congress
  • Place of Presentation: Guangzhou(China)
  • Year and Date: 2011-04-21
• [Presentation] Some neuroprotective mathods for spinal cord injury (2011)
  • Author(s): H.Baba, K.Uchida, H.Nakajima, S.Watanabe, N.Takeura, T.Yayama
  • Organizer: The 13rd Intedrnational Southern China Cardiology Congress
  • Place of Presentation: Guangzhou (China)(招待講演)
  • Year and Date: 2011-04-21
• [Presentation] Cell death-associated genes expression patterns using microarray analysis in rat cultured spinal cord cells exposed to cyclic tensile stresses in vitro (2010)
  • Author(s): Uchida K, Nakajima H, Hirai T, Yayama T, Sugita D, Kobayashi S, Baba H
  • Organizer: 7^<th>Combined Meeting of ORS
  • Place of Presentation: Kyoto (Japan)
  • Year and Date: 2010-10-17
• [Presentation] Cell death-associated genes expression patterns using microarray analysis in rat cultured spinal cord cells exposed to cyclic tensile stresses in vitro (2010)
  • Author(s): K.Uchida, H.Nakajima, T.Hirai, T.Yayama, D.Sugita, S.Kobayashi, H.Baba
  • Organizer: 7^<th>Combined Meeting of ORS
  • Place of Presentation: 京都
  • Year and Date: 2010-10-17
• [Presentation] マイクロアレイを用いたメカニカルストレスに対する脊髄ニューロンの遺伝子発現解析 (2010)
  • Author(s): 内田研造, 中嶋秀明, 彌山峰史, 杉田大輔, 渡邉修司, 馬場久敏
  • Organizer: 第39回日本脊椎脊髄病学会
  • Place of Presentation: 高知
  • Year and Date: 2010-04-23