Analysis of cognitive dysfunction and intracerebral capillary density during multidisciplinary treatment of brain tumors

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07609
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Nagasaki International University
• Principal Investigator: Takai Nobuhiko 長崎国際大学, 薬学部, 教授 (70373389)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 放射線脳壊死 / 高次脳機能障害 / 炭素線治療 / 重粒子線治療

Outline of Final Research Achievements

We developed the HPLC method for the determination of six amino acids and related compounds;glycine , serine, aspartic acid, glutamic acid, taurine, and γ-aminobutyric acid;in the mouse with pre-column derivatization with fluorogenic reagent, NBD-F (4-Fluoro-7-nitrobenzofurazan). After carbon-ion irradiation, the concentration of taurine significantly decreased with time. Taurine, a sulfur-containing amino acid-related compound, has been reported to have a radioprotective effect. Therefore, the decrease in Tau concentration was inferred to be a decrease in radioprotective ability in the mouse. On the contrary, the concentration of Glu significantly increased with time dependence by the irradiation. These results suggested that the increase in glutamate concentration after irradiation induces the activation of NMDA receptors; thus, radiation-induced intestinal injuries could be suppressed by NMDA receptor antagonists as radioprotective agents after carbon-ion irradiation.

Free Research Field

放射線医療学

Academic Significance and Societal Importance of the Research Achievements

放射線による脳や小腸（腸管）の組織障害において、炭素線照射による興奮性アミノ酸や抑制性アミノ酸の経時的変化をHPLC(高速液体クロマトグラフィー)によって一斉分析を行なったことで、細胞壊死に関わるNMDA受容体の活性化にはグルタミン酸の有意な増加と抑制性アミノ酸GABAの減少が伴っていることが明らかとなった。このことは、脳腫瘍放射線治療後に生じる高次脳機能の低下や放射線脳壊死を防ぐためには、NMDA受容体の活性化の効率的に抑制する必要があることを示唆しており、これらの研究成果によって、NMDA受容体の活性化を防ぐ防護薬の最適投与時間の推定が可能となったと考えられる。