Date of Award

2011

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Neuroscience

Abstract

Among the various peripheral nervous system injuries seen clinically, facial nerve lesions are prevalent and have significant functional and emotional impact on patients. As injuries can occur in different segments of the facial nerve and lead to different pathophysiological outcomes, animal models that mimic the common sites of injury need to be developed so that potential therapies can be appropriately investigated. The extratemporal facial nerve axotomy model, in which the nerve is crushed at its exit from the skull, has been well established in the past and used to study the regeneration program of motoneurons. The present study uses this rat injury model to evaluate the therapeutic potential of two treatments, testosterone and nerve electrical stimulation (ES), alone and in combination.

Results demonstrate that ES reduced the delay before sprout formation begins and led to rapid upregulation of regeneration-associated genes, testosterone accelerated the overall regeneration rate and led to delayed but more sustained gene upregulation, and the combinatorial treatment strategy had the most enhanced effects on regeneration events. A more clinically relevant model of facial nerve injury, in which the nerve is crushed during its course in the temporal bone, was also developed and found to lead to substantially prolonged functional recovery times as compared to an extratemporal facial nerve crush. Finally, the combinatorial treatment of ES plus testosterone accelerated functional recovery following the more proximal, intratemporal crush injury. In conclusion, the present study characterizes two models of facial nerve injury and suggests that a combinatorial treatment strategy of ES plus testosterone holds significant clinical potential.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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