Date on Master's Thesis/Doctoral Dissertation
Physiology and Biophysics
Physiology and Biophysics, PhD
spinal cord injury; stretching; inactivity; exercise; recovery
Spinal cord injury (SCI) is a devastating, life altering event that affects approximately 282,000 Americans. The most obvious side effect of SCI is paralysis due to damage to the spinal cord that disrupts ascending and descending pathways as well as central pattern generating circuitry. In addition to paralysis, patients suffer from other debilitating side effects including altered cardiovascular function, autonomic dysreflexia, neuropathic pain, spasticity, and contractures. In contrast to humans, rodents display spontaneous locomotor recovery following incomplete SCI due to in-cage activity/training. Previously, our laboratory has studied the effect of lack of in-cage training by utilizing custom designed rodent wheelchairs. The immobilized SCI animals had poor locomotor function and developed muscle contractures. Additional work by our lab was done to help alleviate the contractures by using clinically-modeled hindlimb stretching. It was found that clinically modeled stretching of rats with a thoracic SCI does not prevent contractures and surprisingly, causes a dramatic decrease in locomotor function that can persist even after stretching is stopped. Most recently, it has been discovered by our lab that stretching is dependent upon the presence of C-fibers (nociceptive afferents), as injured, stretched animals depleted of TRPV1+ C-fibers do not experience such dramatic detriments to their locomotor recovery. Increased sprouting of these nociceptive afferents occurs spontaneously after injury and has been associated with a myriad of other issues, such as autonomic dysreflexia and neuropathic pain. However, recent work has shown that nociceptive afferent sprouting can be prevented or reduced with increased activity and exercise. These findings are significant because stretch-based physical therapy is the most common approach for treating spasticity, contractures, and combating muscle atrophy after spinal cord injury in patients. The work presented in this dissertation aims to clarify the potential mechanisms for stretch-induced locomotor dysfunction in rodent models as well as provide rationale for future clinical and translational research that will be able to determine whether stretching has a negative impact in humans post-SCI. The following experiments revealed that the additional of applied exercise to the stretching protocol does not prevent locomotor dysfunction or the sprouting of nociceptive afferents. We also discovered that stretching animals with high thoracic contusion injuries similarly causes a drastic drop in locomotion, but with some key differences in ability to recover locomotor ability. Our studies suggest that stretching is likely maladaptive for functional locomotor recovery after SCI regardless of injury location or activity status.
Cesarz, Greta M., "Defining the impact of clinically modeled hindlimb stretching, exercise, & inactivity on functional recovery after spinal cord injury." (2022). Electronic Theses and Dissertations. Paper 4018.
Retrieved from https://ir.library.louisville.edu/etd/4018