| Project Area | Inducing lifelong plasticity (iPlasticity) by brain rejuvenation: elucidation and manipulation of critical period mechanisms |
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| Project/Area Number |
20H05922
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| Research Category |
Grant-in-Aid for Transformative Research Areas (A)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (III)
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
阿部 弘基 横浜市立大学, 医学部, 助教 (40737409)
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| Project Period (FY) |
2020-11-19 – 2025-03-31
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| Project Status |
Completed (Fiscal Year 2024)
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| Budget Amount *help |
¥123,370,000 (Direct Cost: ¥94,900,000、Indirect Cost: ¥28,470,000)
Fiscal Year 2024: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2023: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2022: ¥23,010,000 (Direct Cost: ¥17,700,000、Indirect Cost: ¥5,310,000)
Fiscal Year 2021: ¥21,840,000 (Direct Cost: ¥16,800,000、Indirect Cost: ¥5,040,000)
Fiscal Year 2020: ¥32,500,000 (Direct Cost: ¥25,000,000、Indirect Cost: ¥7,500,000)
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| Keywords | AMPA受容体 / GABA受容体 / 脳卒中 / リハビリテーション / 臨界期 / PET / E-I balance / PETイメージング |
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| Outline of Research at the Start |
脳卒中後には機能回復がみられる「臨界期」が存在する. この臨界期の生物学的な根拠はヒトでは明らかにされていない. 本研究では, ヒト生体脳で興奮-抑制バランス(E/I balance)を代替的に測定する方法を興奮性AMPA受容体PETと抑制性GABA受容体を組み合わせて確立する. さらにヒト脳卒中患者でのE/I balanceと機能回復程度との関係を調べ, 生涯可塑性誘導の生物学的根拠を解明する.
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| Outline of Final Research Achievements |
[11C]K-2 AMPA-PET imaging was conducted in nine patients with post-stroke hemiparesis prior to a one-month inpatient rehabilitation program. The severity of upper limb paresis was assessed using the Fugl-Meyer Assessment for the Upper Extremity (FMA-UE). Voxel-wise analysis revealed that baseline SUVRs, referenced to whole-brain uptake, were positively correlated with subsequent changes in ΔFMA-UE. Significant clusters demonstrating this positive correlation were identified in the anterior cingulate cortex and frontal lobe. In a separate cohort of thirteen patients with post-stroke hemiparesis, [11C]K-2 AMPA-PET imaging was performed both before and after a one-month course of inpatient rehabilitation. Voxel-wise analysis of ΔSUVR, normalized to whole-brain uptake, revealed that increases in SUVR were positively correlated with improvements in FMA-UE scores. Brain regions exhibiting significant positive correlations included the anterior cingulate cortex and primary motor areas.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は, 成人の脳卒中患者のリハビリによる麻痺の回復過程において, ヒト生体脳内の可塑的変化をAMPA受容体量の変化から説明した点が新しい. これまで, 可塑的変化の分子実態の多くは, 培養細胞やモデル動物で明らかにされてきたが, ヒト生体脳内での可塑的変化の実態を分子レベルで説明している点はhuman pathophysiologyを理解する上で, 極めて重要な進展であった. こうしたヒト生体脳内での可塑的過程の理解は新しいリハビリ促進薬創薬やdecvice-aidedなリハビリ手法の開発の基盤となる.
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