Analysis of regenerative axonal circuit after spinal cord injury and the effectiveness of p38 MAPK inhibitor

• Project/Area Number: 24592200
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Ehime University
• Principal Investigator: MORINO Tadao 愛媛大学, 医学部附属病院, 講師 (20380248)
• Co-Investigator(Kenkyū-buntansha): OGATA Tadanori 愛媛大学, 大学院医学系研究科, 准教授 (30291503)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: p38 MAPK inhibitor / spinal cord injury / microglia / apoptosis / regeneration / tracer / spinel cord injury / p38 MAPK / behavior / neural network

Outline of Final Research Achievements

We tested the effect of p38 MAPK inhibitor on hindlimb motor function after spinal cord contusion injury in rat and carried out studies on behavior and histological analysis. The damage of hindlimb motor function was reduced with intrathecally administrated p38 MAPK inhibitor from 2 to 6 weeks after injury. The result of present study indicated that the inhibitory mechanisms of spinal cord damage were 1) inhibition of inflammation including microglial proliferation, 2) inhibition of apoptosis on axons and 3) following acceleration of axonal regeneration. We confirmed these results with experiments using neuronal tracer.

Research Products

• [Journal Article] P38 mitogen-activated protein kinase inhibition reduces chondroitin sulfate proteoglycan production after spinal cord injury in rats (2014)
  • Author(s): Yamaoka S, Morino T, Ogata T, Horiuchi H, Miura H
  • Journal Title: Research -an open-access journal Volume: 1 Pages: 802-802
  • DOI: 10.13070/rs.en.1.802
  • Peer Reviewed / Open Access
• [Journal Article] 脊髄損傷後48時間までのp38 MAPK inhibitor硬膜外投与は後肢運動機能を回復させる (2014)
  • Author(s): 森野忠夫、尾形直則、堀内秀樹、山岡慎大朗、三浦裕正
  • Journal Title: 日本整形外科学会雑誌 Volume: 88
• [Journal Article] Different analgesic effects of adenosine between postoperative and neuropathic pain. (2013)
  • Author(s): Yamaoka G, Horiuchi H, Morino T, Miura H, Ogata T.
  • Journal Title: J Orthop Sci. Volume: 18 Issue: 1 Pages: 130-136
  • DOI: 10.1007/s00776-012-0302-0
  • Peer Reviewed
• [Journal Article] 整形外科分野における神経障害の研究 病態の解明と治療法の開発 (2013)
  • Author(s): 尾形 直則, 森野 忠夫, 堀内 秀樹, 山岡 豪大朗, 三浦 裕正
  • Journal Title: 愛媛医学 Volume: 9 Pages: 171-177
  • Peer Reviewed
• [Presentation] 脊髄損傷後48時間までのp38 MAPK inhibitor硬膜外投与は後肢運動機能を回復させる (2014)
  • Author(s): 森野忠夫、尾形直則、堀内秀樹、山岡慎大朗、三浦裕正
  • Organizer: 日本整形外科学会
  • Place of Presentation: 鹿児島県鹿児島市
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] P38 Mitogen activated protein kinase inhibitor ameliorates motor function by inhibition of chondroitin sulfate proteoglycans after spinal cord injury in rat (2014)
  • Author(s): Tadao Morino, Tadanori Ogata, Hideki Horiuchi, Shintaro Yamaoka, Hiromasa Miura
  • Organizer: EUROSPINE
  • Place of Presentation: Lyon, France
  • Year and Date: 2014-09-30 – 2014-10-03
• [Presentation] A novel thermoelectric cooling device using Peltier modules for inducing local hypothermia of the spinal cord: the effect of local electrically-controlled cooling for the treatment of spinal cord injuries in conscious rats. (2012)
  • Author(s): Tadao Morino, Tadanori Ogata, Hideki Horiuchi, Gotaro Yamaoka, Kei Morizane, Hiromasa Miura
  • Organizer: ISCOS (International Spainal Cord Injury Society) meeting
  • Place of Presentation: London, UK