Novel thherapeutic strategy against ischemic stroke based on glial cell interaction by ketone bodies
| Project/Area Number |
15K09324
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安部 貴人 大阪市立大学, 大学院医学研究科, 准教授 (30365233)
中原 仁 慶應義塾大学, 医学部(信濃町), 助教 (60537950)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ケトン体 / βヒドロキシ酪酸 / アストログリア / ミクログリア / 脳虚血モデル / フマル酸ジメチル / アストロサイト / オリゴデンドロサイト / 髄鞘イメージング / 一酸化窒素 / ＴＬＲ４ / 脳虚血 |
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| Outline of Final Research Achievements |
Astroglia produce and release ketone bodies, especially beta-hydroxybutyrate (BHB) by ischemic insult. BHB plays a neuroprotective role in various neurological disorders. Dimethyl fumarate (DMD), used as a disease modifying drug for multiple sclerosis patients, has been found to be a ligand of HCAR2. BHB also acts as a ligand for HCAR2. We have hypothesized that astroglia-derived BHB reduces infarct volume and improves neurological function after a transient middle cerebral artery occlusion (tMCAO). tMCAO was performed in male C57BL/6 mice and Nrf2-/- mice. Infarct volume and neurological function assessed by hanging wire test was significantly improved by DMF treatment both in C57BL/6 mice and in Nrf2-/- mice, suggestive of a Nrf2-independent mechanism. In cultured central nervous system cells, DMF upregulated the expression HO-1 which is most common downstream gene of Keap1 / Nrf2 system. Importantly, however, both BHB and DMF may play neuroprotective roles through HCAR2.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] q-Space Myelin Map imaging for longitudinal analysis of demyelination and remyelination in multiple sclerosis patients treated with fingolimod: A preliminary study2017
Author(s)
Mariko Tanikawa, Jin Nakahara, Junichi Hata, Shigeaki Suzuki, Kanehiro Fujiyoshi, Hirokazu Fujiwara, Suketaka Momoshima, Masahiro Jinzaki, Masaya Nakamura, Hideyuki Okano, Shinichi Takahashi, Norihiro Suzuki
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Journal Title
J Neurol Sci
Volume: 15
Pages: 352-357
DOI
Related Report
Peer Reviewed
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[Journal Article] Application of q-Space Diffusion MRI for the Visualization of White Matter2016
Author(s)
Fujiyoshi K, Hikishima K, Nakahara J, Tsuji O, Hata J, Konomi T, Nagai T, Shibata S, Kaneko S, Iwanami A, Momoshima S, Takahashi S, Jinzaki M, Suzuki N, Toyama Y, Nakamura M, Okano H.
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Journal Title
Journal of Neuroscience
Volume: 36(9)
Issue: 9
Pages: 2796-2808
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] Cytoprotective role of microglia-derived nitric oxide induced by TLR4 stimulation in concert with astroglial pentose-phosphate pathway activation through the Keap1/Nrf2 system.2017
Author(s)
Shinichi Takahashi, Takuya Iizumi, Kyoko Mashima, Kazushi Minami, Yoshikane Izawa, Takato Abe, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki
Organizer
BRAIN & BRAIN PET 2017(28th Symposium on Cerebral Blood Flow, Metabolism and Function/13th Conference on Quantification of Brain Function with PET) April 1-4, 2017, Berlin, Germany
Related Report
Int'l Joint Research
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[Presentation] Activated microglia enhance astroglial neuroprotective pentose-phosphate pathway through the activation of the Keap1/Nrf2 system by nitric oxide.2017
Author(s)
Shinichi Takahashi, Takuya Iizumi, Kyoko Mashima, Kazushi Minami, Yoshikane Izawa, Takato Abe, Takako Hishiki, Makoto Suematsu, Mayumi Kajimura, Norihiro Suzuki
Organizer
XXIII World Congress of Neurology (WCN2017) Sept 16-21, 2017, Kyoto, Japan
Related Report
Int'l Joint Research
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[Presentation] Metabolic balance of neuron, glia and vessel.2015
Author(s)
Shinichi Takahashi
Organizer
The XXVIIth International Symposium on Cerebral Blood Flow, Metabolism and Function & XIIth International Conference on Quantification of Brain Function with PET
Place of Presentation
バンクーバー（カナダ）
Year and Date
2015-06-27
Related Report
Int'l Joint Research / Invited
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