Effects of electrical stimulation and gonadal steroids on rat facial nerve regenerative properties

Issue title: Anniversary Issue: Celebrating 20 years of Restorative Neurology and Neuroscience

Article type: Research Article

Authors: Sharma, Nijee | Coughlin, Lisa | Porter, Ryan G. | Tanzer, Lisa | Wurster, Robert D. | Marzo, Sam J. | Jones, Kathryn J.^{; ;} | Foecking, Eileen M.

Affiliations: Neuroscience Program, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA | Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA | Department of Otolaryngology – Head & Neck Surgery, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA | D Services, Edward Hines, Jr. VA Hospital, Hines, IL, USA

Note: [] Corresponding author: Nijee Sharma, Hines VA Hospital, 5000 South 5th Ave., Bldg. 1, Room A241A, Hines, IL 60141-3030, USA. Tel.: +1 708 202 5719; Fax: +1 708 202 2327; E-mail: nijeesharma@gmail.com

Abstract: Purpose: The neurotherapeutic effects of nerve electrical stimulation and gonadal steroids have independently been demonstrated. The purpose of this study was to investigate the therapeutic potential of a combinatorial treatment strategy of electrical stimulation and gonadal steroids on peripheral nerve regeneration. Methods: Following a facial nerve crush axotomy in gonadectomized adult male rats, testosterone propionate (TP), dihydrotestosterone (DHT), or estradiol (E_{2}) was systemically administered with/without daily electrical stimulation of the proximal nerve stump. Facial nerve outgrowth was assessed at 4 and 7 days post-axotomy using radioactive labeling. Results: Administration of electrical stimulation alone reduced the estimated delay in sprout formation but failed to accelerate the overall regeneration rate. Conversely, TP treatment alone accelerated the regeneration rate by ∼10% but had no effect on the sprouting delay. Combining TP with electrical stimulation, however, maintained the enhanced rate and reduced the sprouting delay. DHT treatment alone failed to alter the regeneration rate but combining it with electrical stimulation increased the rate by 10%. E_{2} treatment alone increased the regeneration rate by ∼5% but with electrical stimulation, there was no additional effect. Conclusions: Electrical stimulation and gonadal steroids differentially enhanced regenerative properties. TP, an aromatizable androgen, augmented regeneration most, suggesting a synergism between androgenic and estrogenic effects. Therapeutically, combining electrical stimulation with gonadal steroids may boost regenerative properties more than the use of either treatment alone.

Keywords: Peripheral nerve injury, regeneration, electrical stimulation, gonadal steroids

DOI: 10.3233/RNN-2009-0489

Journal: Restorative Neurology and Neuroscience, vol. 27, no. 6, pp. 635-646, 2009