REGAIN: Harnessing Sensory Regeneration for Bladder Control in Spinal Cord Injury

Neurogenic bladder dysfunction is a debilitating complication of several common neurological disorders including diabetes mellitus, multiple sclerosis, Parkinson’s disease, and spinal cord injury (SCI), and affecting millions of individuals worldwide. This condition often results in urinary incontinence, recurrent urinary tract infections, and progressive kidney damage, severely impacting quality of life. While extensively studied in the context of SCI, the mechanisms driving sensory dysfunction, particularly the degeneration of Aδ fibers that innervate the bladder, remain poorly understood. This project aims to challenge the presumed causal link between SCI-induced neurogenic bladder dysfunction and Aδ fiber degeneration by combining advanced in vitro and in vivo neuro-urological models. We will first establish a novel neural-bladder co-culture system to explore the direct interactions between bladder tissue and sensory neurons. Concurrently, we will apply in vivo sensory fiber tracing in an SCI model to selectively visualize and monitor Aδ fibers innervating the bladder. Through these complementary systems, we will characterize the timeline and mechanisms of Aδ fiber degeneration associated with neurogenic bladder dysfunction. In parallel, we will evaluate innovative therapeutic strategies, including electrical stimulation, small molecule treatments, and botulinum toxin application, using organ bath analysis of bladder strips from SCI and control animals to assess functional recovery and neuroprotection. To gain deeper insight into the molecular underpinnings of pathology and therapy, we will perform single nucleus