Login to Access Video or Poster Abstract: MP82-03
Sources of Funding: NIH P01 DK093424

Introduction

The role of brain-derived neurotrophic factor (BDNF) in lower urinary tract dysfunction induced by spinal cord injury (SCI) is still unclear. Previous data showed that the neutralization of BDNF in SCI mice increased voided volume and improved the voiding efficiency (2016 AUA). BDNF might involve in the voiding phase via Aδ-fiber afferents, on which the receptor of BDNF (tropomyosin receptor kinase B) is mainly distributed. Acid-sensing ion channels (ASIC), which can function as mechanosensors, are identified as a target of BDNF signaling. We therefore investigated the changes of urethral function and ASIC expression in dorsal root ganglia (DRG) after the neutralization of BDNF in SCI mice.

Methods

Female C57 BL/6N mice underwent Th8-9 spinal cord transection. Three weeks later, an osmotic pump was placed subcutaneously to administer 10µg/kg/hr of anti-BDNF antibody for 1 week. Four weeks after spinal cord transection, SCI mice were evaluated using single-filling cystometry and external urethral sphincter (EUS)-electromyogram (EMG) under an awake condition. CMG-EMG recordings were used to detect intermittent voiding coincided with reductions in intravesical pressure in CMG traces, which occurred during periods of reduced EUS-EMG activity. We measured voiding contraction time (VT), reduced EMG activity duration (RED) and the ratio of RED to VT. Bladder BDNF was measured and the transcripts of TRPV1 and ASIC1, 2, and 3 of L6/S1 DRG were also evaluated.

Results

Compared to vehicle-treated SCI mice, voided volume was significantly increased and voiding efficiency was significantly better in anti-BDNF antibody-treated SCI mice. In CMG-EMG recordings, the RED was significantly prolonged, and the ratio of RED to VT was significantly greater in anti-BDNF antibody-treated SCI mice than those in vehicle-treated SCI mice. Bladder BDNF levels of SCI mice were significantly increased compared with spinal intact mice, but decreased after anti-BDNF antibody treatment. The transcripts of TRPV1, ASIC2 and 3 were increased in SCI mice compared to spinal intact mice, and anti-BDNF treatment significantly decreased expressions of ASIC2 and 3, but not TRPV1.

Conclusions

BDNF upregulation in the bladder is likely to be involved in dyssynergic activity of the EUS during voiding in association with ASIC overexpression in L6/S1 DRG in SCI mice. Thus, BDNF targeting treatments could be effective for voiding problems such as DSD and inefficient voiding after SCI.

Funding

NIH P01 DK093424