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Ketone bodies promote stroke recovery via GAT-1-dependent cortical network remodeling.

Author information

Affiliations

  • 1. Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
      Authors
    • Lin YH 1
    • Yang D 1
    • Ni HY 1
    • Xu XM 1
    • Wu F 1
    • Lin L 1
    • Huang ZQ 1
    • Li SY 1
    • Jiang PL 1
    • Wu HY 1
    • Chang L 1
    • Luo CX 1
    (12 authors)
  • 2. Department of Neurology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China.
      Authors
    • Chen J 2
    • Sun YY 2
    • Wu J 2
    (3 authors)
  • 3. Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
      Authors
    • Hu B 3
    (1 author)
  • 4. Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China; Institution of Stem Cells and Neuroregeneration, Nanjing Medical University, Nanjing 211166, China.
      Authors
    • Zhu DY 4
    (1 author)

Cell Reports, 21 Mar 2023, 42(4):112294
https://doi.org/10.1016/j.celrep.2023.112294 PMID: 36947544 

Abstract 

Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that β-hydroxybutyrate (β-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of β-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke.

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Read article at publisher's site: https://doi.org/10.1016/j.celrep.2023.112294

Read article for free, from open access legal sources, via Unpaywall: http://www.cell.com/article/S2211124723003054/pdfUnpaywall

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    Funding 

    Funders who supported this work.

    Collaborative Innovation Center for Cardiovascular Disease Translational Medicine

      National Key Research and Development Program of China

        National Key Research and Development Program of China Stem Cell and Translational Research (1)

        • Grant ID: 2021YFA1101803

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        National Natural Science Foundation of China (5)

        • Grant ID: 82171368

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        • Grant ID: 81801221

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        • Grant ID: 81870912

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        • Grant ID: 82171293

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        • Grant ID: 82090042

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        Natural Science Foundation of Jiangsu Province (2)

        • Grant ID: BK20191500

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        • Grant ID: BK20211255

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