AB297. SPR-24 Spinal cord injury and detrusor PDGFRα⁺ cells

Objective: Neurogenic bladder dysfunction due to spinal cord injury (SCI) poses a significant threat to the well-being of patients. The complications of this condition include but not are limited to incontinence, renal impairment, urinary tract infection, stones, and poor quality of life. Clinical manifestations of SCI involve combination of storage and voiding bladder problems. Although a number of clinical studies have reported overactive bladder (OAB) after SCI, the pathophysiological mechanisms remain unclear. SCI is widely used to induce neurogenic bladder in rodent models. These animals exhibited dysfunctional condition results in different symptoms, ranging from acute urinary retention to an OAB or a combination of both. There is an abundance of PDGFRα⁺ cells in detrusor muscles. This cell involves the membrane stabilization via activation of SK channels in detrusor PDGFRα⁺ cells during filling. Thus we investigate the molecular and protein expression of PDGFRα⁺ cells from SCI mice to characterize the role of these cells that contributes to development of OAB in SCI.

Methods: SCI was induced by complete compression of T12-L1 spinal cord. Experiments were performed on 24, 48 and 72 hr after surgery. We employed molecular approaches and ex vivo cystometry. Pdgfrα and Kccn1−3 transcripts were analyzed for molecular expression. Ex vivo compliance was used for testing SK channel sensitivity in control and SCI mice.

Results: In quantitative analysis of transcripts, Pdgfrα and Kcnn3 transcripts in SCI detrusor were significantly decreased in a time-dependent manner after SCI surgery compared with control detrusor. In ex vivo cystometry, SCI bladder revealed an increase in the amplitude and frequency of non−voiding pressure responses during filling. Effects of a SK blocker (apamin) and a SK channel activator (SKA-31) were reduced in non-voiding contractions in SCI mice compared to control.

Conclusions: These findings support that downregulation of PDGFRα⁺ cells and SK channels in SCI detrusors might involve the development of OAB in SCI.

Funding Source(s): NIDDK, RO1 DK098388

Keywords: Spinal cord injury (SCI); interstitial cells; ex vivo; cystometry; gene expression