Effects of exercise training on urinary tract function after spinal cord injury

Abstract

Spinal cord injury (SCI) causes dramatic changes in the quality of life, including coping with bladder dysfunction which requires repeated daily and nightly catheterizations. Our laboratory has recently demonstrated in a rat SCI model that repetitive sensory information generated through task-specific stepping and/or loading can improve nonlocomotor functions, including bladder function (Ward PJ, Herrity AN, Smith RR, Willhite A, Harrison BJ, Petruska JC, Harkema SJ, Hubscher CH. J Neurotrauma 31: 819-833, 2014). To target potential underlying mechanisms, the current study included a forelimb-only exercise group to ascertain whether improvements may be attributed to general activity effects that impact target organ-neural interactions or to plasticity of the lumbosacral circuitry that receives convergent somatovisceral inputs. Male Wistar rats received a T9 contusion injury and were randomly assigned to three groups 2 wk postinjury: quadrupedal locomotion, forelimb exercise, or a nontrained group. Throughout the study (including preinjury), all animals were placed in metabolic cages once a week for 24 h to monitor water intake and urine output. Following the 10-wk period of daily 1-h treadmill training, awake cystometry data were collected and bladder and kidney tissue harvested for analysis. Metabolic cage frequency-volume measurements of voiding and cystometry reveal an impact of exercise training on multiple SCI-induced impairments related to various aspects of urinary tract function. Improvements in both the quadrupedal and forelimb-trained groups implicate underlying mechanisms beyond repetitive sensory information from the hindlimbs driving spinal network excitability of the lumbosacral urogenital neural circuitry. Furthermore, the impact of exercise training on the upper urinary tract (kidney) underscores the health benefit of activity-based training on the entire urinary system within the SCI population.

Keywords: bladder; contusion; kidney; locomotor training.

Fig. 1.

Timeline. Experimental procedures and treadmill training are indicated relative to the time when the spinal cord injury (SCI) was made (day 0). See the text for additional definitions.

Fig. 2.

Pretraining group data. Post hoc analysis of the computer-generated IH impactor parameters [force (A); displacement (B)] indicate that there were no significant differences among the 3 groups of animals for extent of injury (as anticipated with randomization). The data in A and B are consistent with the lack of functional differences in the bladder (C; maximum residual volume collected from each rat on day 4) and overground locomotion (D) among the groups before the initiation of training, as it is known that larger residual volumes and lower Basso-Beattie-Bresnahan open-field locomotor test results are reflective of greater injury severities (91). SCI (nontrained); SCI+QT (quadrupedal trained); SCI+FT (forelimb-only trained). Values are means ± SE.

Fig. 3.

SCI-induced polyuria. Total urine volume increased significantly post-SCI (*P < 0.05) but was significantly lower after 9 wk of either SCI+QT or SCI+FT but still significantly above baseline (#P < 0.05). The average volume per void was also significantly greater after SCI (*P < 0.05), although posttraining only the nontrained (NT) SCI group had a further increase in average void volume (#P < 0.05). There were no differences found in the total number of urine events or water intake, suggesting that the higher voiding volume for the NT group after training compensated for the higher 24-h production of urine. Note that the surgical sham group was not subjected to this time-consuming testing as each animal served as its own control (i.e., pre-SCI baseline). Values are means ± SE.

Fig. 4.

Twenty-four-hour micturition cycle. Shown are representative total 24-h urine events measured with the CLAMS system for 2 rats, 1 from the SCI control group (A) and 1 from the SCI+QT group (B). Each plotted line represents a different time point of the experiment; preinjury baseline (●); 2 wk postinjury (pretraining; ○); 6 wk postinjury (4-wk posttraining time point in B; ▲); 10 wk postinjury (8-wk post-training time point in B; △). Each individual symbol represents a single urine event that is a cumulative total over the 24-h period. The horizontal bar represents the 12-h phase when the housing facility lights are off (active period). Note that the majority of urine events occur during the active phase.

Fig. 5.

Terminal awake cystometry. Shown are raw recordings of fill/void cycles from each group of animals. In A, 5 full fill/void cycles are shown for a QT animal. In B, a representative example of 1 fill/void cycle (note the scale bar) is provided for each group (different QT animal from A), and the maximum amplitude values are shown (mmHg). The group means of the averaged data is graphed in C. Significant group differences are shown relative to shams (#) and relative to nontrained SCI animals (*, **). Values are means ± SE.

Fig. 6.

Bladder tissue analysis. Bladder weight but not the ratio of collagen to elastin differed significantly at the 12-wk post-SCI time point relative to noninjured surgical shams. No differences were found between the trained and nontrained SCI groups. Values are means ± SE.

Fig. 7.

Kidney transforming growth factor (TGF)-β and CD11b levels. A: representative examples of kidney TGF-β and CD11b expression levels. B: both SCI+QT and SCI+FT groups had similar expression of TGF-β relative to surgical sham controls. Note that although the SCI trained group levels showed a trend toward sham, they were not significantly different from the nontrained SCI group. C: expression of CD11b was significantly higher relative to shams for all SCI groups, regardless of training. Values are means ± SE. *Significant difference (P < 0.05).

Fig. 8.

Lesion histology. No differences were found between the trained and nontrained groups of injured animals at the 12-wk post-SCI time point. Values are means ± SE.