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Chronic muscle recordings reveal recovery of forelimb function in spinal injured female rats after cortical epidural stimulation combined with rehabilitation and chondroitinase ABC

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)2055-2076
Number of pages22
JournalJournal of Neuroscience Research
Volume100
Issue number11
DOIs
PublishedNov 2022

Bibliographical note

Funding Information: This work was supported by the International Spinal Research Trust (NRB113 to EJB and SBM) and the United Kingdom Medical Research Council (Senior Non‐Clinical Fellowship Award G1002055 to EJB). We thank Ashvin Sehgal for assisting with behavioral data collation, Dorota Sobekova for assisting with bicep mapping studies and Katerina Palios for assisting with imaging. We would especially like to acknowledge Steve (Mac) McMahon, who sadly passed away in October 2021. We thank him for his input into this project and the countless others that he contributed to with his immense knowledge, electrophysiology expertise and for his continuous advice and support, always given so generously. Publisher Copyright: © 2022 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.

King's Authors

Abstract

Cervical level spinal cord injury (SCI) can severely impact upper limb muscle function, which is typically assessed in the clinic using electromyography (EMG). Here, we established novel preclinical methodology for EMG assessments of muscle function after SCI in awake freely moving animals. Adult female rats were implanted with EMG recording electrodes in bicep muscles and received bilateral cervical (C7) contusion injuries. Forelimb muscle activity was assessed by recording maximum voluntary contractions during a grip strength task and cortical motor evoked potentials in the biceps. We demonstrate that longitudinal recordings of muscle activity in the same animal are feasible over a chronic post-injury time course and provide a sensitive method for revealing post-injury changes in muscle activity. This methodology was utilized to investigate recovery of muscle function after a novel combination therapy. Cervical contused animals received intraspinal injections of a neuroplasticity-promoting agent (lentiviral-chondroitinase ABC) plus 11 weeks of cortical epidural electrical stimulation (3 h daily, 5 days/week) and behavioral rehabilitation (15 min daily, 5 days/week). Longitudinal monitoring of voluntary and evoked muscle activity revealed significantly increased muscle activity and upper limb dexterity with the combination treatment, compared to a single treatment or no treatment. Retrograde mapping of motor neurons innervating the biceps showed a predominant distribution across spinal segments C5–C8, indicating that treatment effects were likely due to neuroplastic changes in a mixture of intact and injured motor neurons. Thus, longitudinal assessments of muscle function after SCI correlate with skilled reach and grasp performance and reveal functional benefits of a novel combination therapy.

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