A 2004 survey of individuals with spinal cord injury (SCI), published in the Journal of Neurotrauma, reveals that bladder dysfunction is among the highest priorities after injury, yet few studies are being done. Our study uses a clinically relevant chronic SCI animal model that is geared toward restoring bladder function post-SCI. SCI results in detrimental effects on the upper and lower urinary tract and loss of bladder control affects independence, overall health, and self-image. Current attempts at treatments with various drugs and surgeries have unwanted side effects and limited success. Our goal is to provide a natural therapeutic alternative using body weight-supported treadmill training. We have clinical observations from patients that step training can have beneficial outcomes on bladder maintenance and that there is an interaction between walking and the bladder. It is also known that exercise and activity dependent tasks are highly influential on a family of molecules called neurotrophic factors. Therefore, we will also study the effects of training on nerve growth factor, one member of the neurotrophin family that has been shown to be particularly indicative of bladder dysfunction after SCI. We envision a therapeutic intervention involving a complement of neurotrophic factors and some form of at-home stepping exercise, as most SCI patients do not have easy access to trained therapists on a daily basis. Thus, we propose to study the effects of step training on bladder function in a clinically relevant animal model to identify the mechanisms involved. Each part of this study is specifically designed to be applicable to the SCI patient with the intent of taking the results back to the clinical setting by the end of the 3-year funding period. SCI individuals for those human studies will be recruited from the Frazier Rehabilitation Institute patient base in collaboration with clinical faculty in the Department of Urology at the University of Louisville School of Medicine.