Date of Award

2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Cell Biology, Neurobiology and Anatomy

Abstract

As functional recovery following peripheral nerve injury is dependent upon successful regeneration and target reconnection, combinatorial treatments that enhance different regeneration events may be required for recovery from severe injuries. The neurotherapeutic effects of electrical stimulation (ES) and gonadal steroids have been demonstrated independently and in combination in extratemporal and intratemporal facial nerve injuries. The goals of the first aim were to develop a reliable intracranial facial nerve crush model and to investigate the therapeutic potential of combining ES with testosterone propionate (TP) in this most proximal injury model. Adult male rats were divided into intracranial sham-operated, intracranial crush, and intracranial crush plus ES+TP combination therapy groups. Animals were observed daily for return of facial nerve function and motor nerve conduction studies were done weekly to quantify the return of electrical conduction. Rats treated with the combination therapy recovered partial facial function before untreated rats, suggesting that the combination works in tandem to boost regenerative properties.

To begin to determine the generalizability of this treatment strategy, the second aim of this dissertation investigated the effects of ES and TP on recovery from a recurrent laryngeal nerve (RLN) crush. Following a left RLN crush at the level of the 7th tracheal ring, gonadectomized adult male rats were administered only ES, only TP, a combination of both, or left untreated and vocal fold mobility was assessed weekly. Treatments were found to accelerate recovery individually as well as in combination.

The purpose of the third aim was to further assess the effects of the combination therapy by comparing functional recovery in two types of injury to the sciatic nerve with or without ES plus TP. The sciatic crush injury was compared to a surgery mimicking an autograft procedure of the sciatic nerve (double transection-repair). Adult male rats were divided into four experimental groups: sciatic crush, sciatic crush with ES+TP treatment, sciatic transection-repair (autograft), and autograft with ES+TP. Animals' gaits were observed with the CatWalk system at 2, 4, 8, and 16 weeks post-operative (wpo). Rats treated with the combination therapy recovered partial function earlier than untreated rats in both injury paradigms.

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