BDNF is reportedly involved in changes in neural pathways to induce lower urinary tract (LUT) dysfunction such as detrusor overactivity (DO) and inefficient voiding due to detrusor-sphincter dyssynergia (DSD) following spinal cord injury (SCI). We recently reported that the neutralization of BDNF for 28-day SCI mice improved the voiding efficiency in association with increased synergistic activity of external urethral sphincter during voiding, although it did not influence the non-voiding contraction (NVC) (2017 ICS). However, it has not been well clarified how BDNF affect storage and voiding functions after SCI. Therefore, we investigated the time course of urodynamic function and the expression of BDNF in mice after SCI.

SCI was produced by complete transection of the Th8/9 spinal cord in female C57BL/6N mice. After spinal transection, their bladder was manually squeezed to eliminate the urine once daily until the evaluation. We evaluated the bladder function and bladder BDNF concentration of spinal intact normal mice and SCI mice at 5-day (only BDNF assay), 10-day, 20-day, and 30-day after the injury. Each mouse was evaluated using single-filling cystometry under an awake condition. After the urodynamic evaluation, the bladder was removed and separated into bladder mucosa and muscle layers to measure BDNF levels by the ELISA method and to compare with those of spinal intact mice.

Compared to spinal intact mice, the number of NVC per void and threshold pressure was gradually and significantly increased with time after SCI. The number of NVC of 30-day SCI mice was significantly larger than that of 10-day SCI mice. The voiding pressure among any SCI groups was similar and significantly larger than that of spinal intact mice. The voided volume of 10-day SCI mice was smaller than that of spinal intact mice, 20-day and 30-day SCI mice. Post-void residual (PVR) and bladder capacity were larger in three SCI groups of mice than those of spinal intact mice, and these were larger in 20- and 30-day SCI mice than those of 10-day SCI mice. Voiding efficiency among any SCI groups was similar and significantly smaller than that of spinal intact mice (Figure 1: Urodynamic results). 
   BDNF in the bladder mucosa of any SCI groups was higher than that of spinal intact mice, but BDNF in the bladder muscle was similar between SCI and spinal intact mice. Bladder mucosal BDNF was at the maximum level at 5-day after SCI (Figure 2: Bladder BDNF concentration).

In this study, bladder mucosal BDNF reached its maximal expression levels at 5-day during the 30-day period after SCI, indicating that bladder BDNF expression is elevated in the early phase after SCI. The voided volume was small only at 10-day after SCI. As the time goes on, bladder capacity and PVR were becoming larger with making the voiding efficiency worse. Combined with our previous research, increased BDNF has a significant role in the voiding dysfunction such as dyssynergistic activity of external urethral sphincter from the early phase through the late phase after SCI. The incidence of NVC was gradually increased, and at 30-day after SCI, the number of NVC was larger than that of 10-day SCI mice, suggesting that bladder BDNF does not influence directly on the emergence of NVC because the bladder BDNF concentration was lower at 30-day than at 5-day or 10-day of SCI. The urodynamic changes by the early inhibition of BDNF will provide further insights into the role of BDNF in SCI-induced LUT dysfunction in future.

The early elevation of bladder mucosal BDNF after SCI induces the voiding dysfunction including a small voided volume and poor voiding efficiency. However, the bladder BDNF level may not influence the emergence of NVC, directly.