Effects of blood inflammatory marker and anticoagulant drugs on the blood-brain barrier

• Project/Area Number: 26860177
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Fukuoka University
• Principal Investigator: DOHGU Shinya 福岡大学, 薬学部, 准教授 (60399186)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血液脳関門 / CRP / IL-18 / IL-1β / TNF-α / 血液細胞 / 脳血管内皮細胞 / CD36

Outline of Final Research Achievements

Cerebral microbleeds (CMBs) occurs at the capillaries where the blood-brain barrier (BBB) exists. Dysfunction of the BBB allows extravasation of red blood cells. Therefore, the BBB disruption would be a starting point of CMBs. The aim of this study is to elucidate the effects of anticoagulant drugs and blood inflammatory markers associated with CMBs on the BBB. Major findings of this study are follows; (1) C-reactive protein and interleukin (IL)-18, which are elevated in the patients with CMBs, did not disrupt the BBB, (2) Inflammatory cytokines IL-1β and TNF-α impaired brain endothelial barrier through ERK1/2 activation and increased expression of ICAM-1, VCAM-1 and CD36 in brain endothelial cells, (3) an novel oral anticoagulant drug dabigatran induced the BBB hyperpermeability without affecting tight junction protein expression, but apixaban and rivaroxaban enhanced the BBB function, (4) macrophage-brain endothelial cell adhesion might decrease occludin expression.

Research Products

• [Journal Article] Brain pericytes regulate the blood-brain barrier function (2015)
  • Author(s): Dohgu S, Takata F, Kataoka Y
  • Journal Title: Folia Pharmacologica Japonica Volume: 146 Issue: 1 Pages: 63-65
  • DOI: 10.1254/fpj.146.63
  • NAID: 130005087187
  • ISSN: 0015-5691, 1347-8397
• [Journal Article] Brain pericytes are the most thrombin-sensitive matrix metalloproteinase-9-releasing cell type constituting the blood-brain barrier in vitro. (2015)
  • Author(s): 3.Machida T, Takata F, Matsumoto J, Takenoshita H, Kimura I, Yamauchi A, Dohgu S, Kataoka Y
  • Journal Title: Neurosci Lett. Volume: 599 Pages: 109-114
  • DOI: 10.1016/j.neulet.2015.05.028
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] α7 ニコチン性アセチルコリン受容体によるBBB機能の亢進 (2016)
  • Author(s): 木村郁哉, 道具伸也, 高田芙友子, 松本純一, 川原庸平, 山内淳史, 片岡泰文
  • Organizer: 第136回日本薬学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-26
• [Presentation] 脳ペリサイトのPAR1-PKCδ/θシグナルはトロンビン誘発性MMP-9産生及び血液脳関門障害に関与する (2016)
  • Author(s): 道具伸也, 町田 崇, 高田芙友子, 木村郁哉, 松本純一, 山内淳史, 片岡泰文
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-03-09
• [Presentation] IL-1βおよびTNF-αによる血液脳関門機能障害における細胞内情報伝達機構 (2015)
  • Author(s): 古瀬由奈, 道具伸也, 高田芙友子, 松本純一, 木村郁哉, 吉田 愛, 有留尚孝, 岩尾悠可, 納富 夕, 山内淳史, 片岡泰文
  • Organizer: 第68回日本薬理学会西南部会
  • Place of Presentation: 下関
  • Year and Date: 2015-11-21