Simultaneous administration of IL-3 and GM-CSF ameliorates ischemic brain injury: interaction between brain and bone marrow.

• Project/Area Number: 17K16650
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Ehime University
• Principal Investigator: Choudhury Emamussalehin 愛媛大学, 医学系研究科, 助教(特定教員) (90726803)
• Research Collaborator: TANAKA Junya
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: マイクログリア / 神経細胞 / アポトーシス / 活性酸素 / フローサイトメトリー / CD200 / サイトカイン / 骨髄 / Bcl-xL / マクロファージ / 脳梗塞 / IL-3 / GM-CSF / FACS / 脳血管障害学 / 神経科学 / 免疫学

Outline of Final Research Achievements

The rat middle cerebral artery was transient occluded and stroke model was prepared. The subcutaneous administration of a mixture of IL-3 and GM-CSF from the next day reduced the brain tissue loss and improved cognitive dysfunction. The cytokine mixture increased Bcl-xL expression in neurons but reduce that in microglia. These results suggest that the cytokine mixture inhibited neuronal apoptotic changes, thereby preventing aggravating effects of activated microglia.

Academic Significance and Societal Importance of the Research Achievements

本研究は、脳梗塞後の虚血辺縁部の慢性的な神経細胞死の拡大を防ぐ方法を、サイトカイン投与という形で可能になることを明らかにし、現実的な治療法を提示したことになり、医学医療上の意義は大変大きい。また、脳梗塞後の亜急性期の神経細胞死の原因はよくわかっていなかったが、神経細胞障害が引き金となってマイクログリアの活性化が生じ、そのマイクログリアは抗アポトーシス因子 Bcl-xL発現によって防がれていることを示した意義も大きい。フローサイトメトリーにおいて、CD200をターゲットとして用いれば神経細胞を分離できることを明らかにした点は、今後の研究手法の発展につながる。

Research Products

• [Journal Article] Behavioral tests predicting striatal dopamine level in a rat hemi-Parkinson's disease model (2019)
  • Author(s): Miyanishi, K., Choudhury, M.E., Watanabe, M. et al.
  • Journal Title: Neurochemistry International Volume: 122 Pages: 38-46
  • DOI: 10.1016/j.neuint.2018.11.005
  • Peer Reviewed
• [Journal Article] Chloride intracellular channel protein 2 in cancer and non-cancer human tissues: relationship with tight junctions (2019)
  • Author(s): Yoshitomo Ueno, Saya Ozaki, Akihiro Umakoshi, Hajime Yano, Mohammed E. Choudhury,, et al.
  • Journal Title: Tissue Barriers Volume: article in press Issue: 1 Pages: 1593775-1593775
  • DOI: 10.1080/21688370.2019.1593775
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: a study using a hypnotic bromovalerylurea (2018)
  • Author(s): Abe N, Choudhury ME, Watanabe M, Kawasaki S, Nishihara T, Yano H, Matsumoto S, Kunieda T, Kumon Y, Yorozuya T, Tanaka J
  • Journal Title: Glia Volume: 66(10) Issue: 10 Pages: 2158-2173
  • DOI: 10.1002/glia.23469
  • Peer Reviewed / Open Access
• [Journal Article] Modafinil alleviates levodopa-induced excessive nighttime sleepiness and restores monoaminergic systems in a nocturnal animal model of Parkinson's disease. (2018)
  • Author(s): Rina Ando, Mohammed Emamussalehin Choudhury, et al.
  • Journal Title: Journal of Pharmacological Sciences Volume: 136 Issue: 4 Pages: 266-271
  • DOI: 10.1016/j.jphs.2018.03.005
  • Peer Reviewed / Open Access
• [Journal Article] Sustained anti-inflammatory effects of TGF-β1 on microglia/macrophages. (2018)
  • Author(s): Islam A, Choudhury ME, Kigami Y, Utsunomiya R, Matsumoto S, Watanabe H, Kumon Y, Kunieda T, Yano H, Tanaka J.
  • Journal Title: Biochim Biophys Acta Volume: 1864 (3) Issue: 3 Pages: 721-734
  • DOI: 10.1016/j.bbadis.2017.12.022
  • Peer Reviewed / Open Access
• [Journal Article] Truncated CD200 stimulates tumor immunity leading to fewer lung metastases in a novel Wistar rat metastasis model (2018)
  • Author(s): Kuwabara Jun、Umakoshi Akihiro、Abe Naoki、Sumida Yutaro、Ohsumi Shota、Usa Eika、Taguchi Kana、Choudhury Mohammed E.、Yano Hajime、Matsumoto Shirabe、Kunieda Takeharu、Takahashi Hisaaki、Yorozuya Toshihiro、Watanabe Yuji、Tanaka Junya
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 496 Issue: 2 Pages: 542-548
  • DOI: 10.1016/j.bbrc.2018.01.065
  • Peer Reviewed / Open Access
• [Journal Article] Microglia may compensate for dopaminergic neuron loss in experimental parkinsonism through selective elimination of glutamatergic synapses from the subthalamic nucleus (2017)
  • Author(s): Hitomi Aono, Mohammed Emamussalehin Choudhury, et al.
  • Journal Title: Glia Volume: 65 Issue: 11 Pages: 1833-1847
  • DOI: 10.1002/glia.23199
  • Peer Reviewed
• [Journal Article] Effects of hypnotic bromovalerylurea on microglial BV2 cells (2017)
  • Author(s): Shun Kawasaki, Naoki Abe, Fumito Ohtake, Afsana Islam, Mohammed Emamussalehin Choudhury, et al.
  • Journal Title: Journal of Pharmacological Sciences Volume: 134 Issue: 2 Pages: 116-123
  • DOI: 10.1016/j.jphs.2017.05.007
  • Peer Reviewed / Open Access
• [Presentation] イノシンは、抗炎症効果を与えることによってMPTP処理ドーパミン神経細胞を救済した (2017)
  • Author(s): Choudhury ME, Andoh R, Kyaw WT, Kubo M, Takamoto M, Kannou M, Nishikawa N, Tanaka J, Nagai M, Nomoyo M
  • Organizer: 日本薬理学会西南部会
• [Book] Animal Models for the Study of Human Disease (Second Edition) (2017)
  • Author(s): Neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Animal Models of Parkinson’s Disease
  • Total Pages: 1200
  • Publisher: Academic Press