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

2015 Fiscal Year Final Research Report

• 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
• Keywords: 血液脳関門 / CRP / IL-18 / IL-1β / TNF-α / 血液細胞

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.

Free Research Field

薬理学