Multisystem Neuroprosthetic Training Improves Bladder Function After Severe Spinal Cord Injury

Horst, Maya; Heutschi, Janine; Brand, Rubia van den; Andersson, Karl‐Erik; Gobet, Rita; Sulser, Tullio; Courtine, Grégoire; Eberli, Daniel

doi:10.1016/j.juro.2012.08.200

Cited by 30 publications

(31 citation statements)

References 20 publications

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“…2), most likely reflecting the lowered activation threshold due to the chronic engagement of the neural networks in the trained rats. This result is consistent with the observation that after 8 weeks of locomotor training facilitated by epidural stimulation and pharmacological interventions the contractile responses of the bladder to filling in anesthetized spinal rats were more efficient in trained compared to untrained animals [26]. Direct acute responses to epidural stimulation, however, were not reported.…”

Section: Discussionsupporting

confidence: 91%

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

et al. 2014

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The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

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Section: Discussionsupporting

confidence: 91%

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

et al. 2014

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“…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.…”

supporting

confidence: 60%

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

Hubscher

Montgomery

Fell

et al. 2016

American Journal of Physiology-Renal Physiology

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Hubscher CH, Montgomery LR, Fell JD, Armstrong JE, Poudyal P, Herrity AN, Harkema SJ. Effects of exercise training on urinary tract function after spinal cord injury. Am J Physiol Renal Physiol 310: F1258 -F1268, 2016. First published March 16, 2016 doi:10.1152/ajprenal.00557.2015.-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.bladder; kidney; locomotor training; contusion IMPROVING BLADDER DEFICITS is among the areas of highest priority following spinal cord injury (SCI), as urinary tract impairment has an enormous impact on the quality of life (2,3,26). Life-long urological care is required for SCI individuals, yet most efforts treat symptoms but do not improve intrinsic function (68, 80). Bladder management requires intermittent catheterization throughout the day/night to avoid incontinence, bladder overdistention (which can create high pressure and reflux to the kidneys), inflammation, infections, and autonomic dysreflexia.Despite bladder dysfunction being a high priority for SCI individuals, the focus of health care professionals is on rehabilitation aimed at optimizing mobility and the remaining musculoskeletal function. Locomotor training (L...

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“…The overlap in the neural networks receiving these afferent projections with the networks responsible for controlling LUT function, including bladder and EUS activation, results in both acute as well as chronic changes when these perturbations are used repetitively. Results observed in both animal and human experiments demonstrate the degree to which the neural networks controlling LUT are affected when subjected to locomotor rehabilitation (Gad et al, 2014; Ward et al, 2014; Horst et al, 2013). The physiological responses generated, however, are dependent on the ‘ physiological state of all systems ’.…”

Section: Discussionmentioning

confidence: 97%

“…Animal studies have since begun to address the potential interactions between motor and autonomic functions in response to locomotor training. Interestingly, it has been shown recently that LUT function can be improved in rats undergoing locomotor training (Ward et al, 2014; Horst et al, 2013) that is enabled by the use of ES in combination with the administration of quipazine and strychnine. Specifically, enabling of locomotor-related spinal neuronal circuits by ES can influence neural networks controlling voiding with the onset of bladder emptying within seconds of the onset of the stimulation (Gad et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Neuromodulation of the neural circuits controlling the lower urinary tract

Gad

Roy

Zhong

et al. 2016

Experimental Neurology

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The inability to control timely bladder emptying is one of the most serious challenges among the many functional deficits that occur after a spinal cord injury. We previously demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis and can be used to enable voiding in spinal rats. In the present study, we examined the neuromodulation of lower urinary tract function associated with acute epidural spinal cord stimulation, locomotion, and peripheral nerve stimulation in adult rats. Herein we demonstrate that electrically evoked potentials in the hindlimb muscles and external urethral sphincter are modulated uniquely when the rat is stepping bipedally and not voiding, immediately pre-voiding, or when voiding. We also show that spinal cord stimulation can effectively neuromodulate the lower urinary tract via frequency-dependent stimulation patterns and that neural peripheral nerve stimulation can activate the external urethral sphincter both directly and via relays in the spinal cord. The data demonstrate that the sensorimotor networks controlling bladder and locomotion are highly integrated neurophysiologically and behaviorally and demonstrate how these two functions are modulated by sensory input from the tibial and pudental nerves. A more detailed understanding of the high level of interaction between these networks could lead to the integration of multiple neurophysiological strategies to improve bladder function. These data suggest that the development of strategies to improve bladder function should simultaneously engage these highly integrated networks in an activity-dependent manner.

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Multisystem Neuroprosthetic Training Improves Bladder Function After Severe Spinal Cord Injury

Cited by 30 publications

References 20 publications

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

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

Neuromodulation of the neural circuits controlling the lower urinary tract

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