Basic research on neuroprotective erythropoietin treatment for acute brain disorders

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18362
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55060:Emergency medicine-related
• Research Institution: Nagoya City University
• Principal Investigator: Tamura Tetsuya 名古屋市立大学, 医薬学総合研究院(医学), 講師 (90381889)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: エリスロポエチン / ミクログリア / 脳低温療法 / 脳保護 / 急性脳障害

Outline of Final Research Achievements

After stimulating the microglial cell line BV-2 cells with LPS, the suppression of inflammatory cytokines, iNOS expression, and NF-κB pathway were observed and phagocytosis was decreased in a low temperature environment of 33.5 °C. In addition, co-culture of BV-2 cells and neurons after LPS stimulation suppressed neuronal damage in a low temperature environment. EPO gene expression was enhanced when astrocytes were made hypoxic and sugar-free, and EPO expression was significantly increased at low temperatures. It was also suggested that HIF2α contributed significantly to the expression of EPO in astrocyte. Furthermore, the addition of a condition medium from astrocytes in a low temperature environment to hypoxic and sugar-free neurons suppressed the apoptosis of the neurons.

Free Research Field

救急・集中治療

Academic Significance and Societal Importance of the Research Achievements

ミクログリア活性化調節に注目した脳保護の研究は少ない。今まで明らかにされていないEPOの神経保護効果のメカニズムを、ミクログリアに存在するEPORとの関係から明らかにすることが本研究の特色であり、非常に学術的独自性が高い。EPO製剤による神経保護は臨床応用へ安全に橋渡しができる。一方で、低温環境でのミクログリア活性抑制、アストロサイトからの内因性EPO増加を証明した。救急集中治療領域における脳低温療法の作用機序の解明、EPO治療との組み合わせという意味でも本研究の意義は大きい。