Improving hindlimb locomotor function by Non-invasive AAV-mediated manipulations of propriospinal neurons in mice with complete spinal cord injury View Full Text


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Article Info

DATE

2021-02-03

AUTHORS

Benedikt Brommer, Miao He, Zicong Zhang, Zhiyun Yang, Jessica C. Page, Junfeng Su, Yu Zhang, Junjie Zhu, Emilia Gouy, Jing Tang, Philip Williams, Wei Dai, Qi Wang, Ryan Solinsky, Bo Chen, Zhigang He

ABSTRACT

After complete spinal cord injuries (SCI), spinal segments below the lesion maintain inter-segmental communication via the intraspinal propriospinal network. However, it is unknown whether selective manipulation of these circuits can restore locomotor function in the absence of brain-derived inputs. By taking advantage of the compromised blood-spinal cord barrier following SCI, we optimized a set of procedures in which AAV9 vectors administered via the tail vein efficiently transduce neurons in lesion-adjacent spinal segments after a thoracic crush injury in adult mice. With this method, we used chemogenetic actuators to alter the excitability of propriospinal neurons in the thoracic cord of the adult mice with a complete thoracic crush injury. We showed that activating these thoracic neurons enables consistent and significant hindlimb stepping improvement, whereas direct manipulations of the neurons in the lumbar spinal cord led to muscle spasms without meaningful locomotion. Strikingly, manipulating either excitatory or inhibitory propriospinal neurons in the thoracic levels leads to distinct behavioural outcomes, with preferential effects on standing or stepping, two key elements of the locomotor function. These results demonstrate a strategy of engaging thoracic propriospinal neurons to improve hindlimb function and provide insights into optimizing neuromodulation-based strategies for treating SCI. More... »

PAGES

781

References to SciGraph publications

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    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-021-20980-4

    DOI

    http://dx.doi.org/10.1038/s41467-021-20980-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1135074084

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/33536416


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    346 Spaulding Rehabilitation Hospital, Boston, MA, USA
    347 rdf:type schema:Organization
    348 grid-institutes:grid.4367.6 schema:alternateName Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA
    349 schema:name Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA
    350 F.M. Kirby Neurobiology Center, Boston Children’s Hospital, and Departments of Neurology and Ophthalmology, Harvard Medical School, Boston, MA, USA
    351 rdf:type schema:Organization
     




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