Drug development of central nervous system diseases using dynamic three-dimensional in vitro blood-brain barrier model

• Project/Area Number: 20KK0254
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 90:Biomedical engineering and related fields
• Research Institution: Nagasaki University
• Principal Investigator: 諸藤 陽一 長崎大学, 病院(医学系), 講師 (40437869)
• Co-Investigator(Kenkyū-buntansha): 中川 慎介 福岡大学, 薬学部, 准教授 (10404211) ; 藤本 隆史 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (00712085) ; 佐藤 慧 長崎大学, 医歯薬学総合研究科(医学系), 研究協力員 (40849486) ; 松永 裕希 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (80772136)
• Project Period (FY): 2020-10-27 – 2026-03-31
• Project Status: Granted (Fiscal Year 2022)
• Budget Amount: ¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000); Fiscal Year 2025: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2024: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2023: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 血液脳関門 / ドラッグリポジショニング / 中枢神経薬剤開発 / 血液脳関門モデル / 脳虚血 / ぺリサイト / がん / 脳卒中 / in vitro model / 初代培養細胞 / drug repositioning

Outline of Research at the Start

血液脳関門（BBB）は脳の恒常性保持に重要な役割を果たしている一方、 薬剤開発の観点からは、BBBが治療薬剤の通過を阻むこととなり、中枢神経疾患治療薬開発 の大きな障壁となっている。我々は灌流型3次元共培養in vitro BBBモデルを利用し、病態モデルを作製、neurovascular unitにおける細胞間相互作用を検討する。さらにドラッグリポジショニングの観点から現在臨床の現場で使用されている薬剤がBBBに与える影響及びその作用機序の解明を行う。このメカニズムを解明することにより中枢神経疾患治療薬の開発、ひいては全く新しい創薬概念である「BBB保護薬」の開発 につなげたいと考えている。

Outline of Annual Research Achievements

灌流型3次元血液脳関門モデルの開発においては、内皮細胞、ペリサイト及びアストロサイトを培養した上で灌流することに成功した。不死化ヒト細胞、ラット 初代培養細胞、ヒト初代培養全てにおいて、モデル内に細胞を生着、培養できることを確認した。また、本研究過程において、①霊長類（サル）の初代培養細胞 のみで構成された共培養モデルの特徴、②造影剤による血液脳関門破壊について脳血管内皮細胞内のMAP Kinase pathwaysの関与、③脂質異常症治療薬である pitavastatinが炎症刺激による血液脳関門破壊に拮抗的に働くこと、④Rho kinase阻害薬が血液脳関門保護に働くことについて、見出し、それぞれの知見を英文学術誌において報告した。さらに、本研究過程で得た知見を踏まえ、総説’Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer’を執筆し、スタチンの多面的作用及び心血管、脳血管及び癌に与える影響をまとめ、発表した。本研究及び付随する成果を国内外の学会、研究会で発表するだけでなく、2023年3月には、5th Mini-symposium on the Blood-Brain Barrier: from Basic to Clinical Researchを主催し、世界各国の研究者との意見交換し、今後の研究の方向性も討議した。本研究課題の根幹であるドラッグリポジショニングに関しては、候補薬剤の選定を終え、実験を開始している。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

灌流型3次元血液脳関門モデルの開発は順調に進んでおり、十分に実用可能な段階に到達している。しかし、実験で使用する薬剤及び細胞がCOVID-19の影響で一 部調達できなかったため、一部の実験が施行できなかった。代替として、2次元モデルを使用し、薬剤が血液脳関門に与える影響を検討、解析した。今後は3次元モデルを使用し、2次元モデルで得られた結果との比較を行っていく予定である。

Strategy for Future Research Activity

我々のもつ血液脳関門における初代培養細胞を使用した血液脳関門モデルの技術と米国ワシントン大学、ハンガリー科学アカデミーの学際的ネットワークを融合させることで、研究を飛躍的に発展させていく。

Research Products

• [Int'l Joint Research] ワシントン大学(米国)
• [Int'l Joint Research] セゲド大学(ハンガリー)
• [Int'l Joint Research] スロバキア科学アカデミー(スロバキア)
• [Int'l Joint Research] ワシントン大学(米国)
• [Int'l Joint Research] セゲド大学(ハンガリー)
• [Int'l Joint Research] スロバキア科学アカデミー(スロバキア)
• [Int'l Joint Research] ワシントン大学(米国)
• [Int'l Joint Research] ハンガリー科学アカデミー(ハンガリー)
• [Int'l Joint Research] スロバキア科学アカデミー(スロバキア)
• [Journal Article] Impact of width of susceptibility vessel sign on recanalization following endovascular therapy (2023)
  • Author(s): Kanamoto Tadashi、Tateishi Yohei、Yamashita Kairi、Furuta Kanako、Torimura Daishi、Tomita Yuki、Hirayama Takuro、Shima Tomoaki、Nagaoka Atsushi、Yoshimura Shunsuke、Miyazaki Teiichiro、Ideguchi Reiko、Morikawa Minoru、Morofuji Yoichi、Horie Nobutaka、Izumo Tsuyoshi、Tsujino Akira
  • Journal Title: Journal of the Neurological Sciences Volume: 446 Pages: 120583-120583
  • DOI: 10.1016/j.jns.2023.120583
  • Peer Reviewed / Open Access
• [Journal Article] Case report: Unruptured small middle cerebral artery aneurysm with perianeurysmal edema (2023)
  • Author(s): Goto Yoshihiro、Morofuji Yoichi、Shiozaki Eri、Uchida Daiki、Kawahara Ichiro、Ono Tomonori、Haraguchi Wataru、Tsutsumi Keisuke
  • Journal Title: Frontiers in Surgery Volume: 10
  • DOI: 10.3389/fsurg.2023.1134231
  • Peer Reviewed / Open Access
• [Journal Article] Endovascular Coil Embolization for Recurrent Bow Hunter's Stroke (2022)
  • Author(s): Kutsuna Fumiya、Morofuji Yoichi、Shiozaki Eri、Uchida Daiki、Tokuda Masahiro、Iwanaga Hiroshi、Ono Tomonori、Kawahara Ichiro、Haraguchi Wataru、Tsutsumi Keisuke
  • Journal Title: Internal Medicine Volume: 61 Issue: 23 Pages: 3595-3598
  • DOI: 10.2169/internalmedicine.8906-21
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2022-12-01
  • Peer Reviewed / Open Access
• [Journal Article] Stem Cell Therapy for Acute/Subacute Ischemic Stroke with a Focus on Intraarterial Stem Cell Transplantation: From Basic Research to Clinical Trials (2022)
  • Author(s): Yamaguchi Susumu、Yoshida Michiharu、Horie Nobutaka、Satoh Katsuya、Fukuda Yuutaka、Ishizaka Shunsuke、Ogawa Koki、Morofuji Yoichi、Hiu Takeshi、Izumo Tsuyoshi、Kawakami Shigeru、Nishida Noriyuki、Matsuo Takayuki
  • Journal Title: Bioengineering Volume: 10 Issue: 1 Pages: 33-33
  • DOI: 10.3390/bioengineering10010033
  • Peer Reviewed / Open Access
• [Journal Article] Subarachnoid hemorrhage due to a craniocervical junction arteriovenous fistula associated with thrombus formation in the internal jugular vein: illustrative case (2022)
  • Author(s): Shiozaki Eri、Morofuji Yoichi、Kutsuna Fumiya、Uchida Daiki、Kawahara Ichiro、Ono Tomonori、Haraguchi Wataru、Tsutsumi Keisuke
  • Journal Title: Journal of Neurosurgery: Case Lessons Volume: 4 Issue: 12
  • DOI: 10.3171/case22278
  • Peer Reviewed / Open Access
• [Journal Article] Ruptured basilar artery perforator aneurysm: a novel mechanism of pure subarachnoid hemorrhage in moyamoya disease. Illustrative case (2022)
  • Author(s): Okamura Kazuaki、Higuchi Taro、Izumo Tsuyoshi、Takahira Ryotaro、Sadakata Eisaku、Yoshida Michiharu、Yamaguchi Susumu、Morofuji Yoichi、Baba Shiro、Hiu Takeshi、Matsuo Takayuki
  • Journal Title: Journal of Neurosurgery: Case Lessons Volume: 4 Issue: 8
  • DOI: 10.3171/case22238
  • Peer Reviewed / Open Access
• [Journal Article] RNA Sequencing Data Analysis on the Maser Platform and the Tag-Count Comparison Graphical User Interface (2022)
  • Author(s): Ujifuku Kenta、Morofuji Yoichi、Masumoto Hiroshi
  • Journal Title: Methods Mol Biol Volume: － Pages: 157-170
  • DOI: 10.1007/978-1-0716-2513-2_13
  • ISBN: 9781071625125, 9781071625132
  • Peer Reviewed / Open Access
• [Journal Article] Effects of fasudil on blood?brain barrier integrity (2022)
  • Author(s): Sato Kei、Nakagawa Shinsuke、Morofuji Yoichi、Matsunaga Yuki、Fujimoto Takashi、Watanabe Daisuke、Izumo Tsuyoshi、Niwa Masami、Walter Fruzsina R.、Vigh Judit P.、Santa-Maria Ana Raquel、Deli Maria A.、Matsuo Takayuki
  • Journal Title: Fluids and Barriers of the CNS Volume: 19 Issue: 1 Pages: 43-43
  • DOI: 10.1186/s12987-022-00336-w
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A Spontaneous Extracranial Internal Carotid Artery Dissection with Autosomal Dominant Polycystic Kidney Disease: A Case Report and Literature Review (2022)
  • Author(s): Izumo Tsuyoshi、Ogawa Yuka、Matsuo Ayaka、Okamura Kazuaki、Takahira Ryotaro、Sadakata Eisaku、Yoshida Michiharu、Yamaguchi Susumu、Tateishi Yohei、Baba Shiro、Morofuji Yoichi、Hiu Takeshi、Anda Takeo、Matsuo Takayuki
  • Journal Title: Medicina Volume: 58 Issue: 5 Pages: 679-679
  • DOI: 10.3390/medicina58050679
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Pre-operative Embolization With Onyx for Brain Arteriovenous Malformation Surgery (2022)
  • Author(s): Izumo Tsuyoshi、Okamura Kazuaki、Takahira Ryotaro、Matsunaga Yuki、Sadakata Eisaku、Maeda Hajime、Yamaguchi Susumu、Baba Shiro、Morofuji Yoichi、Hiu Takeshi、Horie Nobutaka、Anda Takeo、Kitagawa Naoki、Tokunaga Yoshiharu、Hayashi Kentaro、Matsumoto Yasushi、Nagata Izumi、Matsuo Takayuki
  • Journal Title: Frontiers in Neurology Volume: 13 Pages: 1-7
  • DOI: 10.3389/fneur.2022.875260
  • Peer Reviewed / Open Access
• [Journal Article] Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer (2022)
  • Author(s): Morofuji Yoichi、Nakagawa Shinsuke、Ujifuku Kenta、Fujimoto Takashi、Otsuka Kaishi、Niwa Masami、Tsutsumi Keisuke
  • Journal Title: Pharmaceuticals Volume: 15 Issue: 2 Pages: 151-151
  • DOI: 10.3390/ph15020151
  • Peer Reviewed / Open Access
• [Journal Article] Unruptured cerebral aneurysms with the segmental duplicated middle cerebral artery formed a fenestrated structure at origin (2022)
  • Author(s): Shiozaki Eri、Kawahara Ichiro、Uchida Daiki、Morofuji Yoichi、Ono Tomonori、Haraguchi Wataru、Honda Kazuya、Moritsuka Tomoya、Tsutsumi Keisuke
  • Journal Title: Surgical Neurology International Volume: 13 Pages: 33-33
  • DOI: 10.25259/sni_1108_2021
  • Peer Reviewed / Open Access
• [Journal Article] 症例報告 側副血行路起始部(A1)と前交通動脈に未破裂脳動脈瘤を伴う無症候性aplastic or twig-like middle cerebral artery-動脈硬化性頭蓋内血管多発狭窄を合併した1例 (2021)
  • Author(s): 副島 航介、原口 渉、堤 圭介、日宇 健、塩崎 絵理、小川 由夏、伊藤 健大、本田 和也、諸藤 陽一、川原 一郎、小野 智憲
  • Journal Title: BRAIN and NERVE Volume: 73 Issue: 4 Pages: 379-388
  • DOI: 10.11477/mf.1416201771
  • ISSN: 1344-8129, 1881-6096
  • Year and Date: 2021-04-01
  • Peer Reviewed
• [Journal Article] A Case of Invasive Sphenoid Sinus Aspergillosis Presenting as Oculomotor Nerve Palsy in a Healthy Patient (2021)
  • Author(s): FUJIMOTO Takashi、MOROFUJI Yoichi、HIU Takeshi、YOSHIDA Koichi、IZUMIKAWA Koichi、WATANABE Takeshi、MATSUO Takayuki
  • Journal Title: NMC Case Report Journal Volume: 8 Issue: 1 Pages: 343-347
  • DOI: 10.2176/nmccrj.cr.2020-0189
  • NAID: 130008055891
  • ISSN: 2188-4226
  • Peer Reviewed / Open Access
• [Journal Article] Hematoma expansion unrelated to rebleeding in ruptured anterior cerebral artery aneurysms treated by early endovascular embolization (2021)
  • Author(s): Okamura Kazuaki、Morofuji Yoichi、Horie Nobutaka、Izumo Tsuyoshi、Sato Kei、Fujimoto Takashi、Matsuo Takayuki
  • Journal Title: Surgical Neurology International Volume: 12 Pages: 571-571
  • DOI: 10.25259/sni_816_2021
  • Peer Reviewed / Open Access
• [Journal Article] Free-Floating Thrombus in the Carotid Artery Without Atherosclerosis Dissolved by Antithrombotic Therapy (2021)
  • Author(s): Shiozaki Eri、Morofuji Yoichi、Kawahara Ichiro、Tsutsumi Keisuke
  • Journal Title: Neurology India Volume: 5 Pages: 1269-1270
  • Peer Reviewed / Open Access
• [Journal Article] Partial Clipping Occlusion Including Rupture Point Is an Effective Strategy for Ruptured Giant Fusiform Basilar Artery Aneurysm: A Technical Case Report (2021)
  • Author(s): Izumo Tsuyoshi、Fujimoto Takashi、Morofuji Yoichi、Tateishi Yohei、Matsuo Takayuki
  • Journal Title: Frontiers in Neurology Volume: 12 Pages: 743654-743654
  • DOI: 10.3389/fneur.2021.743654
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of a Primate Blood-Brain Barrier Co-Culture Model Prepared from Primary Brain Endothelial Cells, Pericytes and Astrocytes (2021)
  • Author(s): Watanabe Daisuke、Nakagawa Shinsuke、Morofuji Yoichi、Toth Andrea E.、Vastag Monika、Aruga Jun、Niwa Masami、Deli Maria A.
  • Journal Title: Pharmaceutics Volume: 13 Issue: 9 Pages: 1484-1484
  • DOI: 10.3390/pharmaceutics13091484
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Successful Endovascular Treatment for Middle Cerebral Artery Occlusion Caused by the Thrombus Formation in the Pulmonary Vein Stump Following Left Upper Lung Lobectomy (2021)
  • Author(s): Shiozaki Eri、Morofuji Yoichi、Kawahara Ichiro、Tagawa Tsutomu、Tsutsumi Keisuke
  • Journal Title: Cureus Volume: 13 Pages: 17150-17150
  • DOI: 10.7759/cureus.17150
  • Peer Reviewed / Open Access
• [Journal Article] MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood-Brain Barrier Disruption (2021)
  • Author(s): Matsunaga Yuki、Nakagawa Shinsuke、Morofuji Yoichi、Dohgu Shinya、Watanabe Daisuke、Horie Nobutaka、Izumo Tsuyoshi、Niwa Masami、Walter Fruzsina R.、Santa-Maria Ana Raquel、Deli Maria A.、Matsuo Takayuki
  • Journal Title: Pharmaceutics Volume: 13 Issue: 8 Pages: 1272-1272
  • DOI: 10.3390/pharmaceutics13081272
  • NAID: 120007172250
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells (2021)
  • Author(s): Ishii Mitsutoshi、Tsuchiya Tomoshi、Doi Ryoichiro、Morofuji Yoichi、Fujimoto Takashi、Muto Hideki、Suematsu Takashi、Mori Ryoichi、Matsumoto Keitaro、Miyazaki Takuro、Tomoshige Koichi、Watanabe Hironosuke、Iwatake Mayumi、Nagayasu Takeshi
  • Journal Title: Pharmaceutics Volume: 13 Issue: 8 Pages: 1264-1264
  • DOI: 10.3390/pharmaceutics13081264
  • NAID: 120007172252
  • Peer Reviewed / Open Access
• [Journal Article] Pitavastatin Ameliorates Lipopolysaccharide-Induced Blood-Brain Barrier Dysfunction (2021)
  • Author(s): Fujimoto Takashi、Morofuji Yoichi、Kovac Andrej、Erickson Michelle A.、Deli Maria A.、Niwa Masami、Banks William A.
  • Journal Title: Biomedicines Volume: 9 Issue: 7 Pages: 837-837
  • DOI: 10.3390/biomedicines9070837
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Unusual course of the vagus nerve passing anterior to the internal carotid artery during carotid endarterectomy (2021)
  • Author(s): Kawahara Ichiro、Shiozaki Eri、Soejima Kosuke、Ogawa Yuka、Morofuji Yoichi、Ono Tomonori、Haraguchi Wataru、Tsutsumi Keisuke
  • Journal Title: Surgical Neurology International Volume: 12 Pages: 278-278
  • DOI: 10.25259/sni_216_2021
  • Peer Reviewed / Open Access
• [Journal Article] Ischemic Stroke as a Warning Sign of Impending Aneurysmal Rupture: A Report of Two Cases (2021)
  • Author(s): OKAMURA Kazuaki、MOROFUJI Yoichi、IZUMO Tsuyoshi、SATO Kei、FUJIMOTO Takashi、HORIE Nobutaka、MATSUO Takayuki
  • Journal Title: NMC Case Report Journal Volume: 8 Issue: 1 Pages: 85-88
  • DOI: 10.2176/nmccrj.cr.2020-0040
  • NAID: 130007995210
  • ISSN: 2188-4226
  • Peer Reviewed / Open Access
• [Journal Article] A1 Segment Unruptured Aneurysm of Persistent Primitive Olfactory Artery Coexisted with Accessory Middle Cerebral Artery (2021)
  • Author(s): Ogawa Yuka、Soejima Kosuke、Kawahara Ichiro、Shiozaki Eri、Morofuji Yoichi、Ono Tomonori、Haraguchi Wataru、Tsutsumi Keisuke
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 30 Issue: 6 Pages: 105758-105758
  • DOI: 10.1016/j.jstrokecerebrovasdis.2021.105758
  • Peer Reviewed / Open Access
• [Journal Article] Carotid Endarterectomy Using Lone Star Retractor System (2021)
  • Author(s): Kawahara Ichiro、Shiozaki Eri、Ogawa Yuka、Morofuji Yoichi、Haraguchi Wataru、Ono Tomonori、Tsutsumi Keisuke、Honda Kazuya、Ito Takehiro
  • Journal Title: Journal of Stroke and Cerebrovascular Diseases Volume: 30 Issue: 5 Pages: 105684-105684
  • DOI: 10.1016/j.jstrokecerebrovasdis.2021.105684
  • Peer Reviewed / Open Access
• [Journal Article] Characteristics of aneurysmal subarachnoid hemorrhage associated with rheumatic disease (2020)
  • Author(s): Yamaguchi Susumu、on behalf of the Nagasaki SAH Registry Study、Horie Nobutaka、Sato Shuntaro、Kaminogo Makio、Morofuji Yoichi、Izumo Tsuyoshi、Anda Takeo、Suyama Kazuhiko、Matsuo Takayuki
  • Journal Title: Neurosurgical Review Volume: － Issue: 5 Pages: 2611-2618
  • DOI: 10.1007/s10143-020-01435-8
  • Peer Reviewed / Open Access
• [Journal Article] Exploration of Pericyte-Derived Factors Implicated in Lung Cancer Brain Metastasis Protection: A Pilot Messenger RNA Sequencing Using the Blood?Brain Barrier In Vitro Model (2020)
  • Author(s): Ujifuku Kenta、Fujimoto Takashi、Sato Kei、Morofuji Yoichi、Muto Hideki、Masumoto Hiroshi、Nakagawa Shinsuke、Niwa Masami、Matsuo Takayuki
  • Journal Title: Cellular and Molecular Neurobiology Volume: － Issue: 4 Pages: 997-1004
  • DOI: 10.1007/s10571-020-00988-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comparison of the rate of dedifferentiation with increasing passages among cell sources for an in vitro model of the blood?brain barrier (2020)
  • Author(s): Fujimoto Takashi、Morofuji Yoichi、Nakagawa Shinsuke、Kovac Andrej、Horie Nobutaka、Izumo Tsuyoshi、Niwa Masami、Matsuo Takayuki、Banks William A.
  • Journal Title: Journal of Neural Transmission Volume: 127 Issue: 8 Pages: 1117-1124
  • DOI: 10.1007/s00702-020-02202-1
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Carotid-Carotid Bypass for a Carotid Artery Aneurysm (2020)
  • Author(s): Morofuji Yoichi、Matsunaga Yuki、Izumo Tsuyoshi
  • Journal Title: World Neurosurgery Volume: 138 Pages: 7-8
  • DOI: 10.1016/j.wneu.2020.02.113
  • NAID: 120006988257
  • Peer Reviewed
• [Journal Article] Drug Development for Central Nervous System Diseases Using In Vitro Blood-brain Barrier Models and Drug Repositioning (2020)
  • Author(s): Morofuji Yoichi、Nakagawa Shinsuke
  • Journal Title: Current Pharmaceutical Design Volume: 26 Issue: 13 Pages: 1475-1494
  • DOI: 10.2174/1381612826666200224112534
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pericytes Suppress Brain Metastasis from Lung Cancer In Vitro. (2019)
  • Author(s): Fujimoto, T., Nakagawa, S., Morofuji, Y., Watanabe, D., Ujifuku, K., Horie, N., Izumo, T., Niwa, M., Banks, W. A., Deli, M. A., Matsuo, T.
  • Journal Title: Cell Mol Neurobiol Volume: 40(1) Issue: 1 Pages: 113-121
  • DOI: 10.1007/s10571-019-00725-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] International Collaboration in Science (2023)
  • Author(s): Yoichi Morofuji
  • Organizer: 5th Mini-Symposium on The Blood-Brain Barrier from Basic to Clinical Research
  • Int'l Joint Research / Invited
• [Presentation] 血液脳関門をターゲットとした脳梗塞治療薬の開発Rho-kinase innhibitor動注療法の可能性 (2023)
  • Author(s): 諸藤陽一
  • Organizer: Stroke 2023
• [Presentation] Brain metastases project (2022)
  • Author(s): Yoichi Morofuji
  • Organizer: Guarding the brain; innovative strategies to prevent breast cancer brain metastases (BCBM)
  • Int'l Joint Research / Invited
• [Presentation] Challenges in Drug Development for Central Nervous System Diseases：from the perspective of a neurosurgeon (2022)
  • Author(s): Yoichi Morofuji
  • Organizer: Wurzburg-Nagasaki Symposium
  • Int'l Joint Research / Invited
• [Presentation] Mechanical Thrombectomy For Acute Ischemic Stroke (2021)
  • Author(s): Yoichi Morofuji
  • Organizer: Asian Congress of Neurological Surgeons Seminar
  • Int'l Joint Research / Invited
• [Presentation] 血液脳関門をターゲットとした脳梗塞治療薬の開発 (2021)
  • Author(s): 諸藤陽一、中川慎介、佐藤慧、松永裕希、藤本隆史、堀江信貴、出雲剛、松尾孝之
  • Organizer: 日本脳神経外科学会 第80回学術総会
• [Presentation] Intraarterial therapy of Rho-kinase inhibitor for acute ischemic stroke (2021)
  • Author(s): Morofuji Y, Nakagawa S, Sato K, Matsunaga Y, Fujimoto T, Izumo T, Niwa M, Matsuo T
  • Organizer: The 13th World Stroke Congress
  • Int'l Joint Research
• [Presentation] MRI灌流画像であるarterial spin labelingに基づくtime windowにとらわれない血栓回収療法の治療適応決定 (2021)
  • Author(s): 諸藤陽一、堀江信貴、出雲剛、森川実、立石洋平、辻野彰、松尾孝之
  • Organizer: 第37回日本脳神経血管内治療学会学術総会（シンポジウム）
• [Presentation] Closing remark (2021)
  • Author(s): Yoichi Morofuji
  • Organizer: 4th Mini-symposium on the Blood-Brain Barrier: from Basic to Clinical Research
  • Int'l Joint Research / Invited
• [Presentation] Intraarterial therapy of Rho-kinase inhibitor for acute ischemic stroke (2021)
  • Author(s): Morofuji Y
  • Organizer: 3rd Minisymposium on the blood-brain barrier: from basic to clinical research
  • Int'l Joint Research / Invited
• [Presentation] 急性期脳梗塞治療としてのファスジル動注療法の可能性 (2020)
  • Author(s): 諸藤陽一、中川慎介、藤本隆史、佐藤慧、松永裕希
  • Organizer: 第36回日本脳神経血管内治療学会
• [Presentation] 急性期脳梗塞治療としてのファスジル動注療法の可能性 (2020)
  • Author(s): 諸藤陽一、中川慎介、藤本隆史、佐藤慧、松永裕希
  • Organizer: Stroke2021
• [Book] Biology of Pericytes -Recent Advances (2021)
  • Author(s): Morofuji Y, Nakagawa S, Fujimoto T, Yamaguchi S, Ujifuku K, Matsuo T
  • Total Pages: 278
  • Publisher: Springer Nature
• [Book] Cancer Drug Resistance: Methods and Protocols (2021)
  • Author(s): Kenta Ujifuku, Yoichi Morofuji, Hiroshi Masumoto
  • Total Pages: 100
  • Publisher: Springer Nature
• [Book] The NOVARTIS Foundation (Japan) for the Promotion of Science -Annal Report (2021)- (2021)
  • Author(s): Yoichi Morofuji
  • Total Pages: 150
  • Publisher: The NOVARTIS Foundation
• [Funded Workshop] 5th Mini-symposium on the Blood-Brain Barrier: from Basic to Clinical Research (2023)
• [Funded Workshop] 4th Mini-symposium on the Blood-Brain Barrier: from Basic to Clinical Research (2021)
• [Funded Workshop] 3rd Minisymposium on the blood-brain barrier: from basic to clinical research (2021)