Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

Abstract

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

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

“…Recent animal studies, however, have shown that LT post-SCI also improves bladder function (46,90), a finding consistent with a few reports from human SCI studies (42,48,75). For example, a recent study from our laboratory (90) has shown, using a spinal contusion model in adult male rats, functional gains of lower urinary tract function as assessed with terminal urodynamic measures after 12 wk of daily LT for a period of 60 min/day. The interaction of lower limb musculature with the bladder and its sphincter has been observed sporadically over the years, as far back as 1933, in both humans and animal studies (20,53,74).…”

“…Locomotor training (LT) has emerged as a safe and effective therapy for post-SCI motor deficits with many benefits (cardiovascular function, strength, mobility) (9,23,43,52,84). Recent animal studies, however, have shown that LT post-SCI also improves bladder function (46,90), a finding consistent with a few reports from human SCI studies (42,48,75). For example, a recent study from our laboratory (90) has shown, using a spinal contusion model in adult male rats, functional gains of lower urinary tract function as assessed with terminal urodynamic measures after 12 wk of daily LT for a period of 60 min/day.…”

“…Note that the amounts obtained at a 3-to 4-day time point are reflective of the initial peak bladder dysfunction immediately post-SCI with higher volumes indicative of a more severe injury (91). These data along with a 2-wk time point score of overground locomotion using the 21-point BassoBeattie-Bresnahan (BBB) open-field locomotor test (6) (as previously described in detail) (90,91) were set aside for end-of-study post hoc analysis to check for pretraining group differences in terms of lesion severity. Training was initiated 14 days postinjury after animals were randomly divided into three study groups (as described below).…”

“…SCI rats were randomly divided into 3 groups of 16 each 2 wk postinjury: two groups followed a step-training regimen over a treadmill belt assisted by a body weight support system (Exer-3R treadmill, Columbus Instruments) (90,91), and a nontrained control group used no body support. All groups were harnessed with a cloth rodent vest (Robomedica, Mission Viejo, CA) with spring scales clipped onto both ends of the vest for weight support as needed.…”

“…With respect to the improvements in bladder function with 60 min/day of stepping on a treadmill using body weight support and manual facilitation in a natural position (90), the current study was designed to expand upon our initial findings to include 1) non-weight-bearing stepping with a forelimbs-only exercise group; 2) collection of weekly metabolic cage data to monitor SCI-induced persistent polyuria (overproduction of urine); and 3) further tissue assessments that include the structural integrity of the bladder wall and the impact of training on the upper urinary tract (kidneys).…”