Roles of fibrinolytic system on vascular permeability after ischemic stroke

• Project/Area Number: 15K08194
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Nagahama Institute of Bio-Science and Technology
• Principal Investigator: Nagai Nobuo 長浜バイオ大学, バイオサイエンス学部, 教授 (90260281)
• Research Collaborator: MATANO Yasuki ; ADACHI Yuta ; KIMURA Nanami
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脳梗塞 / 虚血 / 血管透過性 / 血液脳関門 / 線溶系 / プラスミン / 線溶因子 / 組織リモデリング / MMP / マトリックスメタロプロテイナーゼ / プラスミノゲン / ｔPA / uPA

Outline of Final Research Achievements

Roles of plasmin activity associated with ischemic stroke was studied using a mouse brain damage model and brain derived endothelial cell line.
It was found that the sequential reduction of the vascular permeable region size was significantly reduced by gene deficient of plasminogen and plasmin activity was distribute apical side of the vessel at the region where vascular permeability was increased. These findings suggested the involvement of plasmin activity on the remodeling of basal lamina. I was also found that the expression of tight junction molecules in cultured brain derived endothelial cell line was suppressed by hypoxia mimicking oxygen-glucose deprivation treatment but not affected by plasmin treatment. These findings suggested plasmin did not contribute to the blood brain barrier disruption under ischemic condition.

Research Products

• [Int'l Joint Research] University of Exeter Medical School(United Kingdom)
• [Journal Article] Increase in blood-brain barrier permeability does not directly induce neuronal death but may accelerate ischemic neuronal damage (2018)
  • Author(s): Chiemi Ohmori, Yusuke Sakai, Yasuki Matano, Yasuhiro Suzuki, Kazuo Umemura and Nobuo Nagai
  • Journal Title: Experimental Animals Volume: 67 Issue: 4 Pages: 479-486
  • DOI: 10.1538/expanim.18-0038
  • NAID: 40021698493
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] A Review of the Mechanisms of Blood-Brain Barrier Permeability by Tissue-Type Plasminogen Activator Treatment for Cerebral Ischemia. (2016)
  • Author(s): Suzuki Y, Nagai N, Umemura K.
  • Journal Title: Front Cell Neurosci. Volume: -
  • DOI: 10.3389/fncel.2016.00002
  • Peer Reviewed / Open Access
• [Presentation] Reactive oxygen species generation and neural network rearrangement is associated with the increase in vascular permeability after ischemic stroke. (2017)
  • Author(s): 34.Yasuki Matano, Kumiko Takayama, Ryosuke Ohi, Nobuo Nagai
  • Organizer: 第94回日本生理学会大会
  • Place of Presentation: アクトシティ浜松
  • Year and Date: 2017-03-28
• [Presentation] Reactive oxygen species generation and neural network rearrangement is associated with the increase in vascular permeability after ischemic stroke. (2017)
  • Author(s): Yasuki Matano, Kumiko Takayama, Ryosuke Ohi, Nobuo Nagai
  • Organizer: 第94回日本生理学会大会
• [Presentation] 脳梗塞の傷害部位周辺での血管透過性亢進の修復におけるプラスミンの寄与 (2017)
  • Author(s): 足立悠太、湯川直人、鈴木康裕、梅村和夫、永井信夫.
  • Organizer: 第39回日本血栓止血学会学術集会
• [Presentation] Roles of alpha2-antiplasmin on pathogenesis of non-alcoholic steatohepatitis under high-fat diet feeding. (2016)
  • Author(s): Nagai N, Ono M, Utsuno T, Hirata T
  • Organizer: The 1st Joint Meeting of ISFP and PA Workshop
  • Place of Presentation: 日本平ホテル
  • Year and Date: 2016-10-17
• [Presentation] Roles of t-PA/plasmin system on the functional recovery and histological repair after ischemic stroke in mice. (2016)
  • Author(s): Yasuki Matano, Kumiko Takayama, Ryosuke Ohi, Nobuo Nagai
  • Organizer: The 1st Joint Meeting of ISFP and PA Workshop.
  • Place of Presentation: 日本平ホテル
  • Year and Date: 2016-10-17
• [Presentation] Identification of novel substrates of plasmin on endothelial cell. (2016)
  • Author(s): Nanami Kimura, Makoto Hasegawa, Nobuo Nagai.
  • Organizer: The 1st Joint Meeting of ISFP and PA Workshop.
  • Place of Presentation: 日本平ホテル
  • Year and Date: 2016-10-17
• [Presentation] 血管内皮細胞上のα２アンチラスミンの新規の基質の同定 (2016)
  • Author(s): 永井 信夫、木村 七海、長谷川 慎
  • Organizer: 第38回日本血栓止血学会学術集会
  • Place of Presentation: 奈良春日野国際フォーラム
  • Year and Date: 2016-06-16
• [Presentation] α2-アンチプラスミン遺伝子欠損マウスに対する 高脂肪食付与の影響 (2016)
  • Author(s): 小野 雅、永井 信夫
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] 組織型プラスミノゲン活性化因子(tPA)およびプラスミノゲンが脳梗塞の機能学的回復および組織学的修復に及ぼす影響の検討 (2016)
  • Author(s): 酒井祐輔、大森智恵美、永井信夫
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] プラスミンの生理学的新規基質の探索 (2016)
  • Author(s): 木村 七海 長谷川 慎 永井 信夫
  • Organizer: 第93回日本生理学会大会
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2016-03-22
• [Presentation] 血管透過性亢進が脳梗塞に及ぼす影響の検討 (2015)
  • Author(s): 酒井祐輔、大森智恵美、永井信夫
  • Organizer: 第108回近畿生理学談話会
  • Place of Presentation: 近畿大学東大阪キャンパス
  • Year and Date: 2015-10-24
• [Presentation] プラスミンの生理学的新規基質の探索 (2015)
  • Author(s): 木村 七海 長谷川 慎 永井 信夫
  • Organizer: 第108回近畿生理学談話会
  • Place of Presentation: 近畿大学東大阪キャンパス
  • Year and Date: 2015-10-24
• [Presentation] 組織型プラスミノーゲン活性化因子 (tPA)の脳梗塞後の組織的回復への関与の検討 (2015)
  • Author(s): 酒井祐輔、鈴木康裕、梅村和夫、永井信夫
  • Organizer: 第37回日本血栓止血学会学術総会
  • Place of Presentation: 甲府総合市民会館
  • Year and Date: 2015-05-21