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  • Florey Department of Neuroscience and Mental Health
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    Multisensory stimulation improves functional recovery and resting-state functional connectivity in the mouse brain after stroke

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    Author
    Hakon, J; Quattromani, MJ; Sjolund, C; Tomasevic, G; Carey, L; Lee, J-M; Ruscher, K; Wieloch, T; Bauer, AQ
    Date
    2018-01-01
    Source Title
    NeuroImage: Clinical
    Publisher
    ELSEVIER SCI LTD
    University of Melbourne Author/s
    Carey, Leeanne
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Hakon, J., Quattromani, M. J., Sjolund, C., Tomasevic, G., Carey, L., Lee, J. -M., Ruscher, K., Wieloch, T. & Bauer, A. Q. (2018). Multisensory stimulation improves functional recovery and resting-state functional connectivity in the mouse brain after stroke. NEUROIMAGE-CLINICAL, 17, pp.717-730. https://doi.org/10.1016/j.nicl.2017.11.022.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253369
    DOI
    10.1016/j.nicl.2017.11.022
    Abstract
    Stroke causes direct structural damage to local brain networks and indirect functional damage to distant brain regions. Neuroplasticity after stroke involves molecular changes within perilesional tissue that can be influenced by regions functionally connected to the site of injury. Spontaneous functional recovery can be enhanced by rehabilitative strategies, which provides experience-driven cell signaling in the brain that enhances plasticity. Functional neuroimaging in humans and rodents has shown that spontaneous recovery of sensorimotor function after stroke is associated with changes in resting-state functional connectivity (RS-FC) within and across brain networks. At the molecular level, GABAergic inhibitory interneurons can modulate brain plasticity in peri-infarct and remote brain regions. Among this cell-type, a decrease in parvalbumin (PV)-immunoreactivity has been associated with improved behavioral outcome. Subjecting rodents to multisensory stimulation through exposure to an enriched environment (EE) enhances brain plasticity and recovery of function after stroke. Yet, how multisensory stimulation relates to RS-FC has not been determined. In this study, we investigated the effect of EE on recovery of RS-FC and behavior in mice after stroke, and if EE-related changes in RS-FC were associated with levels of PV-expressing neurons. Photothrombotic stroke was induced in the sensorimotor cortex. Beginning 2 days after stroke, mice were housed in either standard environment (STD) or EE for 12 days. Housing in EE significantly improved lost tactile-proprioceptive function compared to mice housed in STD environment. RS-FC in the mouse was measured by optical intrinsic signal imaging 14 days after stroke or sham surgery. Stroke induced a marked reduction in RS-FC within several perilesional and remote brain regions. EE partially restored interhemispheric homotopic RS-FC between spared motor regions, particularly posterior secondary motor. Compared to mice housed in STD cages, EE exposure lead to increased RS-FC between posterior secondary motor regions and contralesional posterior parietal and retrosplenial regions. The increased regional RS-FC observed in EE mice after stroke was significantly correlated with decreased PV-immunoreactivity in the contralesional posterior motor region. In conclusion, experimental stroke and subsequent housing in EE induces dynamic changes in RS-FC in the mouse brain. Multisensory stimulation associated with EE enhances RS-FC among distinct brain regions relevant for recovery of sensorimotor function and controlled movements that may involve PV/GABA interneurons. Our results indicate that targeting neural circuitry involving spared motor regions across hemispheres by neuromodulation and multimodal sensory stimulation could improve rehabilitation after stroke.

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