Roles of sphingosine-1-phosphate on the blood-brain barrier

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462167
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: Nagasaki University
• Principal Investigator: NAKAGAWA Shinsuke 長崎大学, 医歯薬学総合研究科(医学系), 講師 (10404211)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 血液脳関門 / スフィンゴシン1リン酸 / タイトジャンクション / スフィンゴシンキナーゼ / プロブコール / 虚血再灌流 / ABCA1

Outline of Final Research Achievements

The bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P), is known as regulator of many physiological and pathophysiological processes. We examined the effects of S1P on barrier functions using an in vitro blood-brain barrier (BBB) model. S1P decreased transendothelial electrical resistance (TEER) and increased the permeability of sodium fluorescein under normal culture condition. Next, we examined the role of S1P on BBB function under oxygen glucose deprivation (OGD)/ reoxygenation condition. OGD/reoxygenation induced the increment of S1P production in endothelial cells, pericytes and astrocytes. OGD/reoxygenation decreased the BBB barrier function. However, treatment of inhibitors of S1P synthesis enzyme or S1P transporter improved the BBB dysfunction induced by OGD/reoxygenation. Thus, inhibition of S1P signaling is considered to improve blood-brain barrier dysfunction induced by oxygen glucose deprivation.

Free Research Field

血液脳関門学