2023 Fiscal Year Final Research Report

Development of a treatment for chronic stroke by converting reactive astrocytes into astrocytes in the critical period.

Research Project

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Project/Area Number	22K19741
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research Institution	National Rehabilitation Center for Persons with Disabilities
Principal Investigator	Nagao Motoshi 国立障害者リハビリテーションセンター(研究所), 研究所運動機能系障害研究部, 研究部長 (00359671)
Project Period (FY)	2022-06-30 – 2024-03-31
Keywords	グリア細胞 / アストロサイト / 反応性アストロサイト / 脳卒中 / リハビリテーション
Outline of Final Research Achievements	Astrocytes in the postnatal critical period control synapse formation and pruning, possessing a high capacity to reorganize neural circuits. It is believed that in the chronic phase of stroke, the reduced capacity for neural circuit reorganization in reactive astrocytes makes functional recovery through rehabilitation difficult. In this study, I performed a comprehensive gene expression analysis of astrocytes in the critical period, adulthood, and the recovery and chronic phases of stroke, and identified candidate molecules that define the properties of astrocytes in the critical period. In subsequent research, these molecules will be overexpressed in reactive astrocytes in the chronic phase of stroke to convert them into cells similar to those in the critical period. I plan to examine whether this conversion can enhance functional recovery after stroke through rehabilitation by changing the brain environment into one with high neural plasticity.
Free Research Field	神経科学　リハビリテーション医学
Academic Significance and Societal Importance of the Research Achievements	脳卒中の急性期治療の進歩により一命を取りとめる患者の数は増加しているが、その後の重篤な後遺症（麻痺、運動・意識障害、疼痛、失語）に対してはリハビリテーション以外に有効な治療法がないのが現状である。しかし、そのリハビリテーションも受傷後６ヶ月以内の神経可塑性が高い回復期に行わなければ、十分な機能改善が望めない。現在、脳卒中患者の多くは回復期を過ぎた慢性期患者であり、リハビリテーションでさえ有効な治療法とはなり得ない。本研究の成果は、慢性期の脳内環境を神経可塑性が高く、リハビリテーションに再度、応答する状態に変えることのできるリハビリテーション効果促進薬の開発につながることが期待される。