Feasibility Testing of a Novel Combination Therapy To Improve Genitourinary Function Recovery After Spinal Cord Injury in a Rat Model

This SPiRE proposal is aimed at evaluating the feasibility of a novel interventional approach to facilitate urinary bladder function recovery after spinal cord injury (SCI) in a rat model. SCI results in permanent loss of motor and autonomic function (bladder, bowel, and sexual functions) below the level of the lesion due to limited intrinsic healing capacity and the absence of effective therapeutic interventions. SCI involves complex pathophysiology that presents multiple barriers to functional recovery. Despite significant research progress around locomotion, profound SCI-related alterations in autonomic functions have not received a proportional level of scientific urgency. Rehabilitation of these autonomic functions is an understudied field with great relevance to Veterans as successful interventional therapies would significantly improve their quality of life (QOL). There is thus an urgent need to assess the feasibility of new interventions capable of synergistically improving autonomic functional recovery. The objective of this proposal is to evaluate the feasibility of such interventions in a rat model of severe SCI. Our proposal is focused on using principles of regenerative medicine (using neural progenitor cell; NPC graft) in combination with neuromodulation (using trans- spinal magnetic stimulation; TSMS) to provide neuroprotection and promote functional recovery by a synergistic effect in this SCI rat model. Aim 1 will characterize the impact of three different types of SCI that affect urogenital circuits and bladder function recovery. Aim 2 will evaluate if NPC grafts can promote supraspinal (pontine micturition center; PMC) axon regeneration and relay PMC signal into the spinal cord below the injury. In addition, we will assess if neuromodulation using TSMS could strengthen and stabilize the functional connectivity of injured spinal neurons that control bladder function. The proposed work is innovative because it proposes a novel interventional approach capable of synergistically improving the survival and growth of injured neural cells and facilitating neuronal functional connectivity, as well as reducing ischemia and inflammation. This collaborative research will be led and performed by experts in the fields of SCI and Urology, and the overarching goal of this research is to benefit Veterans with SCI.