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Title: The effect of inflammatory cytokines on functional nerve recovery following peripheral nerve injury and repair
Author: Shembesh, Hisham
ISNI:       0000 0004 7428 2186
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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The aim of this research was to investigate the effect of novel cytokine antagonists, tumour necrosis factor-alpha antagonist (Etanercept) and interleukin-1 antagonist (Anakinra), and interleukin-10 anti-inflammatory cytokine on the inflammatory response at the site of peripheral nerve injury, in order to establish their potential contribution on nerve regeneration and determine their potential effect on the reduction or prevention of neuropathic pain. The outcome measures of functional nerve recovery were assessed using a combination of electrophysiology to determine the rate of axon regeneration, immunohistochemistry to study immune cell immunoreactivity and their related pain markers expression, and analysis of gait coordination to determine nerve function. In addition, axonal tracing was used to quantity regenerated nerve fibres following nerve conduit repair. The results showed that the peripheral application of interleukin-1 antagonist and combination treatment of interleukin-10 and tumour necrosis factoralpha antagonist at the time of nerve repair was significantly effective in downregulating macrophage immunoreactivity at the site of nerve injury and repair. Application also decreased expression of GFAP and IBA-1 positive glial cells in the spinal cord. Results showed that interleukin-1 antagonist or tumour necrosis factoralpha antagonist, as single therapies did not appear to significantly improve the regenerative potential of injured axons after nerve repair. However, application of a combined therapy of tumour necrosis factor-alpha antagonist and interleukin-10 greatly improved recovery, possibly due to reduced immune response and scar tissue formation. Following poly-caprolactone nerve conduit repair, axonal tracing revealed that regenerating axons took a more uniform path in the regeneration process, following treatment with tumour necrosis factor-alpha antagonist, when compared with the sterile water treatment, where many axons displayed a disorganized pattern of regeneration. However, no significant difference in nerve function recovery was observed between the two groups. The findings contained in this work provide new insights into the role of inflammatory cytokines on functional nerve recovery and the development of neuropathic pain after peripheral nerve injury. These agents demonstrate potential as therapeutic strategies for the treatment of peripheral nerve injures.
Supervisor: Atkins, Simon ; Bird, Emma ; Boissonade, Fiona Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available