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Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke

Author

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  • Andrew N. Clarkson

    (The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA
    Present address: Departments of Psychology and Anatomy and Structural Biology, University of Otago, PO Box 913, Dunedin 9013, New Zealand.)

  • Ben S. Huang

    (The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA
    The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA)

  • Sarah E. MacIsaac

    (The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA)

  • Istvan Mody

    (The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA
    The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA
    The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA)

  • S. Thomas Carmichael

    (The David Geffen School of Medicine at UCLA, 635 Charles Young Drive South, Los Angeles, California 90095, USA)

Abstract

A target for boosting stroke recovery Stroke is a leading cause of disability because of the brain's limited capacity for recovery. The functional recovery that does occur derives in part from the transfer of brain function to the tissue bordering the stroke site. A study in a mouse model shows that stroke reduces excitation in neurons adjacent to the stroke site by impairing transport of GABA, leading to a build-up of this inhibitory neurotransmitter. Genetic or pharmacological blockade of extrasynaptic GABAA receptors improves behavioural recovery. Critically, the treatment remains successful when there is a delay between stroke and therapy. This work identifies novel pharmacological targets for neural recovery after stroke and possibly other brain injuries.

Suggested Citation

  • Andrew N. Clarkson & Ben S. Huang & Sarah E. MacIsaac & Istvan Mody & S. Thomas Carmichael, 2010. "Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke," Nature, Nature, vol. 468(7321), pages 305-309, November.
    • Handle: RePEc:nat:nature:v:468:y:2010:i:7321:d:10.1038_nature09511
    DOI: 10.1038/nature09511
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    Cited by:

    1. Mohamad Motaharinia & Kim Gerrow & Roobina Boghozian & Emily White & Sun-Eui Choi & Kerry R. Delaney & Craig E. Brown, 2021. "Longitudinal functional imaging of VIP interneurons reveals sup-population specific effects of stroke that are rescued with chemogenetic therapy," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    2. Marcello Massimini & Maurizio Corbetta & Maria V. Sanchez-Vives & Thomas Andrillon & Gustavo Deco & Mario Rosanova & Simone Sarasso, 2024. "Sleep-like cortical dynamics during wakefulness and their network effects following brain injury," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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