2019 Fiscal Year Final Research Report

Establishment of restrative therapy for the hippocampal dysfunction in patients receiving cranial radiotherapy

Research Project

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Project/Area Number	17H01403
Research Category	Grant-in-Aid for Scientific Research (A)
Allocation Type	Single-year Grants
Section	一般
Research Field	Tumor diagnostics
Research Institution	University of the Ryukyus
Principal Investigator	Ishiuchi Shogo 琉球大学, 医学(系)研究科(研究院), 教授 (10312878)
Co-Investigator(Kenkyū-buntansha)	片桐千秋琉球大学, 医学(系)研究科(研究院), 助教 (00443664) 外間洋平琉球大学, 医学(系)研究科(研究院), 助教 (60573318) 西村正彦琉球大学, 医学(系)研究科(研究院), 助教 (60597889)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	バイオマーカー / Chemobrain / 海馬神経新生 / 放射線治療 / 認知能
Outline of Final Research Achievements	Radiotherapy is an important treatment option for central nervous system malignancies, however, cranial radiation induces hippocampal dysfunction and white matter injury, which concomitantly induced higher cognitive dysfunction, resulted in reduced quality of life (QOL) in the patients with brain disorders. Signaling for excitatory amino acids glutamate through N-methyl-D-aspatare receptors (NMDAR) play a central role both in hippocampal neurogenesis, and oligodendrocytes forming myelin sheath in the cerebrum. Treatment by memantine, a non-competitive antagonist for NMDAR, induced amelioration of impaired hippocampal networks of pattern separation detected by functional magnetic resonance imagings. Hyperbaric preconditioning of the patients just before radiotherapy induced restration of white matter damages detected by whole brain analysis with Tract-Based Spacial Statics using by diffusion tensor imaging data. Placebo-controlled trial (Trial ID: jRCTs071190010) is now underway.
Free Research Field	脳神経外科学、神経科学、放射線学
Academic Significance and Societal Importance of the Research Achievements	本研究は、がん治療が及ぼす高次脳機能障害の克服を目指したもので、従来注意を払われてない放射線をはじめとするがん治療が及ぼす認知能障害を明確化し治療戦略の創出を確立した点に学術的意義がある。また社会的にも本研究の成果は, がん治療患者全体に大きなインパクトを与え臨床へフィードバックすることで患者の生活の質を上げることにつながる。がん領域のみならず老化,認知症,うつ病をはじめとする多様な脳疾患における記憶力の改善法-パターン分離能の向上が可能となれば社会全体にとって大きな福音となるに違いない。本研究はその端緒となるものと思われる。