Development of a novel neuroprotection drug for spinal cord injury

• Project/Area Number: 17K10913
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Hokkaido University
• Principal Investigator: Asano Tsuyoshi 北海道大学, 大学病院, 助教 (50722493)
• Co-Investigator(Kenkyū-buntansha): 中川 慎介 長崎大学, 医歯薬学総合研究科(医学系), 講師 (10404211) ; 角家 健 北海道大学, 医学研究院, 特任准教授 (30374276)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 血液脳脊髄関門 / 脊髄損傷 / 神経保護 / ハイスループットスクリーニング / ドラッグリポジショニング / 創薬 / 脳脊髄血液関門 / 血管内皮細胞

Outline of Final Research Achievements

The current study has developed a high-throughput screening assay (HTSA) for identifying drugs to protect the blood brain spinal cord barrier (BBSCB) function. Actual screening of FDA approved drugs by this HTSA identified Berberine as a potential drug to protect BBSCB. Berberine protected BBSCB functions from oxygen-glucose deprivation and reoxygenation stress in vitro coculture model as well as cervical spinal cord injury (SCI) and traumatic brain injury models. Furthermore, Berberine reduced lesion size and neuronal loss and improved gait performances after cervical SCI in mice. The current study established the useful HTSA to find potential neuroprotective drugs by maintaining BBSCB functions and identified Berberine as a novel BBSCB protection drug.

Academic Significance and Societal Importance of the Research Achievements

血液脳脊髄関門は中枢神経に広く分布し、中枢神経の恒常性維持に重要な役割を果たしている。血液脳脊髄関門破綻は脊髄損傷のような外傷のほか、神経免疫疾患、神経変性疾患などの病態の増悪に関与しており、血液脳脊髄関門の機能保護は各種中枢神経疾患の予防および治療のターゲットとなっている。本研究で開発した薬剤スクリーニング方法によって同定された薬剤が、実際に血液脳脊髄関門機能保護を介して、神経保護機能を示したことは、本スクリーニング方法の有用性を示し、中枢神経疾患に対する新規薬剤同定方法になりうると考える。

Research Products

• [Presentation] Development of High-throughput Assay to Screen Potential Drugs to Protect Blood Brain Spinal Cord Barrier Identifies Berberine as Neuroprotection Drug for Spinal Cord Injury. (2020)
  • Author(s): Yuki Suzuki, Ken Kadoya, Takeshi Endo, Yuki Matsui, Yuen Rufei, Tsuyoshi Asano, Shinsuke Nakagawa, Norimasa Iwasaki.
  • Organizer: The 66th Annual Meeting of Orthopaedic Research Society 2020 annual meeting
  • Int'l Joint Research
• [Presentation] Newly Developed High-throughput Screening Assay Identifies Berberine as a Potential Drugs to Protect Blood-Brain Barrier from toxic stresses. (2019)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Rufei Y, Asano T, Nakagawa S, Iwasaki N.
  • Organizer: 1st Mini-symposium on the blood-brain barrier from basic to clinical research
  • Int'l Joint Research
• [Presentation] Drug repositioning for new CNS injury treatment: Targeting on protection of Blood-brain barrier. (2019)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Rufei Y, Asano T, Nakagawa S, Iwasaki N.
  • Organizer: The XIV European Meeting on Glial Cells in Health and Disease,
  • Int'l Joint Research
• [Presentation] ドラッグリポジショニングによる脊髄損傷治療薬の開発：血液脊髄関門機能保護 (2019)
  • Author(s): 鈴木裕貴、角家健、遠藤健、松居祐樹、袁儒非、浅野毅、中川慎介、岩崎倫政
  • Organizer: 第92回日本整形外科学会学術総会
• [Presentation] 血液脊髄関門機能保護に注目した脊髄損傷治療薬の開発 (2019)
  • Author(s): 鈴木裕貴、角家健、遠藤健、松居祐樹、袁儒非、浅野毅、中川慎介、岩崎倫政
  • Organizer: 第38回日本運動器移植・再生医学研究会
• [Presentation] ドラッグリポジショニングによる脊髄損傷治療薬の開発：血液脊髄関門機能保護 (2019)
  • Author(s): 鈴木裕貴、角家健、中川慎介、遠藤健、松居祐樹、袁儒非、浅野毅、岩崎倫政
  • Organizer: 第34回日本整形外科学会基礎学術集会
• [Presentation] 血液脊髄関門機能保護に注目した脊髄損傷治療薬の開発 (2019)
  • Author(s): 鈴木裕貴、角家健、遠藤健、松居祐樹、袁儒非、浅野毅、中川慎介、岩崎倫政
  • Organizer: 第5回北海道大学部局横断シンポジウム
• [Presentation] 血液脳脊髄関門の機能保護に注目した中枢神経保護薬の開発 (2019)
  • Author(s): 鈴木裕貴、角家健、中川慎介、遠藤健、松居祐樹、袁儒非、浅野毅、岩崎倫政
  • Organizer: 第24回グリアクラブ
• [Presentation] Newly Developed High-throughput Screening Assay Identifies Potential Drugs to Protect Blood-Brain Barrier. (2019)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Rufei Y, Asano T, Nakagawa S, Iwasaki N
  • Organizer: 1st Mini-symposium on the blood-brain barrier from basic to clinical research
  • Int'l Joint Research / Invited
• [Presentation] Establishment of High-throughput assay for identifying potential compounds to protect brain endothelial cells from oxidative stress (2018)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Iwasaki N.
  • Organizer: Orthopaedic Research Society 2018 annual meeting
  • Int'l Joint Research
• [Presentation] Newly Developed High-throughput Screening Assay Identifies Potential Drugs to Protect Blood-Brain Barrier. (2018)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Rufei Y, Asano T, Nakagawa S, Iwasaki N
  • Organizer: 1st International Symposium on Signal Transduction at the Blood-Brain Barriers
  • Int'l Joint Research
• [Presentation] Newly Developed High-throughput Screening Assay Identifies Berberine as a Potential Drug to Protect Blood-Brain Barrier from toxic stresses (2018)
  • Author(s): Suzuki Y, Kadoya K, Endo T, Matsui Y, Rufei Y, Asano T, Nakagawa S, Iwasaki N
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] 新規High-throughput screening assayが同定したBerberineの血液脳脊髄関門保護薬としての可能性 (2018)
  • Author(s): 鈴木裕貴、角家健、中川慎介、遠藤健、松居祐樹、袁儒非、浅野毅、岩崎倫政
  • Organizer: 第41回日本神経科学大会