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Title: Investigating human Schwann cell phenotypes and outcome measures of muscle reinnervation
Author: Wilcox, Matthew Benjamin
ISNI:       0000 0005 0288 6930
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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Peripheral Nerve Injury (PNI) often causes partial or complete paralysis and/or loss of sensation of the segment of the body involved. Traumatic PNI is a global problem and can result in significant disability and socio-economic impacts. Clinical translation of new therapeutics for the treatment of PNI is challenged by the little information that is known about the cellular and molecular features that underpin human nerve regeneration. Moreover, clinical models and measurements that can quantify the efficacy of new treatments for PNI are not well established. Therefore, this PhD explored injured and healthy human nerve samples liberated from reconstructive nerve procedures to characterise the cellular and molecular features of human peripheral nerve degeneration. Associated with this theme of characterisation of human nerve injury, the recovery of motor units in reinnervated elbow flexor muscles following nerve transfer was quantified using Motor Unit Number Estimation (MUNE). In order to better understand the relationship of MUNE with the biological process of nerve regeneration, an animal model of nerve injury was used to investigate the association between MUNE and histological markers of regeneration. MUNE was found to be a sensitive marker of muscle reinnervation in human and animal models of nerve regeneration. Moreover, MUNE demonstrated a correlation with histological markers of muscle reinnervation. It is known that these changes in the number of motor units are accompanied by changes in muscle volume. Therefore, using the same surgical scenario of nerve transfer to reanimate elbow flexor muscles, this PhD measured the recovery of muscle volume following nerve transfer to reanimate elbow flexor muscles using quantitative Magnetic Resonance Imaging (MRI) techniques. It was found that MRI assessment of muscle volume is a measure that is sensitive to the biological process of nerve regeneration. With further data, this has the capacity to determine the efficacy of new therapeutics for the treatment of PNI and predict the likely functional recovery following PNI. In summary, the findings represent an important step towards understanding the in vivo cellular and molecular events in human nerve degeneration. In addition, MUNE and quantitative MRI techniques were found to represent sensitive and responsive measures of nerve regeneration. With further data, the findings presented here will help new therapeutic options for human nerve injury advance.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available