The control of neural-glial spinal cells microenvironment after traumatic injury through transfection of neurotrophic factor

• Project/Area Number: 21791389
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: University of Fukui
• Principal Investigator: NAKAJIMA Hideaki University of Fukui, 医学部, 助教 (10397276)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 脊髄損傷 / 神経栄養因子 / 逆行性導入 / 遺伝子治療 / アデノウィルスベクター / アポトーシス / 神経保護 / 軸索再生 / 遺伝子導入 / apoptosis抑制 / 神経保護効果 / 神経再生

Research Abstract

It is very important to deliver the neurotrophins with safety and effectively. Our results suggest that targeted retrograde AdV-BDNF-gene in vivo delivery may enhance neuronal and oligodendroglial survival sustained mechanical compression spinal cord injury. The suppression of apoptosis may one of the mechanism of these positive results. The method is a potentially suitable approach for the delivery of therapeutic genes important to promote the survival of neurons and oligodendroglia after traumatic spinal cord injury.

Research Products

• [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 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 23巻 Pages: 859-866
• [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] Tumor necrosis factor-alpha and its receptors contribute to apoptosis of oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy) sustaining chronic mechanical compression. (2009)
  • Author(s): Inukai T, Uchida K, Nakajima H, Yayama T, Kobayashi S, Mwaka ES, Guerrero AR, Baba H.
  • Journal Title: Spine 34 Pages: 2848-2857
  • NAID: 10027250776
  • Peer Reviewed
• [Journal Article] Updates on ossification of posterior longitudinal ligament.Ossification front of posterior longitudinal ligament and cellular biological assessment of chronic mechanical compressed spinal cord. (2009)
  • Author(s): Uchida K, Nakajima H, Yayama T, Sato R, Baba H.
  • Journal Title: Clin Calcium 19 Pages: 1472-1479
• [Journal Article] Tumor necrosis factor-alpha and its receptors contribute to apoptosis of oligodendrocytes in the spinal cord of spinal hyperostotic mouse (twy/twy) sustaining chronic mechanical compression. (2009)
  • Author(s): Inukai T, Uchida K, Nakaiima H, Yayama T, Kobayashi S, Mwaka ES, Guerrero AR, Baba H.
  • Journal Title: Spine 34 Pages: 2848-2857
  • Peer Reviewed
• [Journal Article] 損傷後頸髄神経細胞に対する逆行性神経栄養因子遺伝子導入 (2009)
  • Author(s): 中嶋秀明, 内田研造, 犬飼智雄, 小林茂, 馬場久敏
  • Journal Title: 中部日本整形外科災害外科学会雑誌 52 Pages: 161-162
• [Journal Article] Updates on ossification of posterior longitudinal ligament. Ossification front of posterior longitudinal ligament and cellular biological assessment of chronic mechanical compressed spinal cord (2009)
  • Author(s): Uchida K, Nakajima H, Yayama T, Sato R, Baba H.
  • Journal Title: Clin Calcium 19 Pages: 1472-1479
• [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 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, Kobayashi S, Ma WY, Liu SY, Zhu P, Baba H.
  • Journal Title: Spine in press
  • NAID: 10030901954
  • 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, Kobayashi S, Ma WY, Liu SY, Zhu P, Baba H.
  • Journal Title: Spine Volume: (in press)
  • NAID: 10030901954
  • Peer Reviewed
• [Presentation] 損傷脊髄におけるHighmobility group box -1(HMGB-1)の動態と役割 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-22
• [Presentation] 損傷脊髄におけるHigh mobility group box-1(HMGB-1)の動態と役割 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-22
• [Presentation] 脊髄損傷に対する移植ヒト骨髄間質細胞の動態と治療効果 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第25回日本整形外科学会基礎学術集会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-21
• [Presentation] 脊髄損傷に対するアデノウィルスベクターを用いた神経栄養因子遺伝子逆行性導入による神経保護効果 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第29回運動器移植・再生医学研究会
  • Place of Presentation: 滋賀
  • Year and Date: 2010-09-25
• [Presentation] (1)脊髄損傷に対するアデノウィルスベクターを用いた神経栄養因子遺伝子逆行性導入による神経保護効果 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第29回運動器移植・再生医学研究会
  • Place of Presentation: 滋賀
  • Year and Date: 2010-09-25
• [Presentation] 脊髄損傷における神経栄養因子遺伝子逆行性導入による神経グリア系細胞の保護効果 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第39回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 高知
  • Year and Date: 2010-04-23
• [Presentation] 慢性脊髄圧迫モデル(twy/twy)に対する神経栄養因子遺伝子導入による再生能力賦活化効果 (2010)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第9回再生医療学会
  • Place of Presentation: 広島
  • Year and Date: 2010-03-19
• [Presentation] Adenovirus-mediated retrograde transfer of neurotrophin-3 gene enhances survival of anterior horn neurons of twy/twy mice with chronic mechanical compression of the spinal cord (2009)
  • Author(s): Uchida K., Nakaiima H., Hirai T., Inukai T., Chen K., Alexander G., Yayama T., Baba H
  • Organizer: 37^<th> Annual Meeting of the Cervical Spine Research Society
  • Place of Presentation: Salt Lake City
  • Year and Date: 2009-12-04
• [Presentation] 慢性脊髄圧迫モデル(twy/twy)に対する逆行性神経栄養因子遺伝子導入を用いたneuronおよびoligodendrocyteの賦活化効果 (2009)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2009-11-06
• [Presentation] 損傷後頚髄に対するBDNF遺伝子逆行性導入を用いたneuronおよびoligodendrocyteの賦活化効果 (2009)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2009-11-05
• [Presentation] 慢性脊髄圧迫モデル(twy/twy)に対する逆行性神経栄養因子遺伝子導入を用いたneuronおよびohgodendrocyteの賦活化効果 (2009)
  • Author(s): 中嶋秀明、内田研造、犬飼智雄、彌山峰史、Chen Kebing、小林茂、馬場久敏
  • Organizer: 第24回日本整形外科学会基礎学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2009-11-05
• [Presentation] 損傷脊髄内神経栄養因子遺伝子逆行性導入による神経グリア系細胞に対する賦活化効果 (2009)
  • Author(s): 中嶋秀明, 他
  • Organizer: 第38回日本脊椎脊髄病学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 2009-04-25