The mechanism of neuroprotection by brain hypothermia in the view of thermal reaction of neurovascular unit

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10939
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology
• Research Institution: Kyushu Women's University
• Principal Investigator: M Tomohiro 九州女子大学, 家政学部, 准教授 (50314828)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 脳低温療法 / T細胞 / パーフォリン / ニューロン死 / 接着因子 / 脳血管内皮細胞 / アポトーシス / ケモカイン

Outline of Final Research Achievements

The underlying mechanisms of therapeutic hypothermia for the neuroprotection are partially understood. Here we examined the effects of hypothermia and hyperthermia on T cell-derived perforin (Pfn) and the expression/production of adhesion molecules and chemokines by brain microvascular endothelial (bEnd.3)cells in an attempt to identify the mechanisms of this therapy. We also evaluated whether Pfn induced death in neuronal cells and bEnd.3 cells.
Consequently, compared with normothermia, Pfn release in T cells was reduced by hypothermia but augmented by hyperthermia. Pfn caused the death of neuronal cells and induced both apoptosis/necrosis in bEnd.3 cells; both effects were concentration-dependent.
In bEnd.3 cells, the mRNA expression of adhesion molecules was reduced by hypothermia compared with normothermia. The production of chemokines was reduced by hypothermia but augmented by hyperthermia.

Free Research Field

神経免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究は、ニューロンの周りに存在し、その死の過程に関与するNeurovascular Unit(NVU)構成細胞の中で、特に、T細胞（広義）と脳血管内皮細胞に着目し、それら由来のニューロン傷害性因子発現に低温・高温が及ぼす影響を調べ、脳低温療法による脳保護機構を説明するものであった。得られた結果の中で、特に、T細胞由来パーフォリン（Pfn）は、血液脳関門（BBB）を構成する脳血管内皮細胞死を誘導した。脳血管内皮細胞死は、血管透過性亢進とBBB崩壊に基づく末梢性炎症細胞の更なる浸潤を伴い、脳障害増悪に繋がるため、Pfnの低温下での産生低下は脳保護機構に非常に重要であることが示唆された。