Activity-Based Training Reverses Spinal Cord Injury-Induced Changes in Kidney Receptor Densities and Membrane Proteins

Gumbel, Jason H.; Montgomery, Lynnette R.; Yang, Cui; Hubscher, Charles H.

doi:10.1089/neu.2019.6670

Cited by 7 publications

(27 citation statements)

References 65 publications

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“…Excessive urine production can further exacerbate an already demanding catheterization schedule and disrupt daily life. We have found that the mechanisms underlying SCI-induced polyuria are multifactorial, including an interplay of various peptides involved in the physiological regulation of fluid balance, plasma volume, and overall urine output (Ward and Hubscher, 2012;Montgomery and Hubscher, 2018;Gumbel et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury

Herrity

Aslan

Ugiliweneza

et al. 2021

Front. Syst. Neurosci.

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Spinal cord injury (SCI) results in profound neurologic impairment with widespread deficits in sensorimotor and autonomic systems. Voluntary and autonomic control of bladder function is disrupted resulting in possible detrusor overactivity, low compliance, and uncoordinated bladder and external urethral sphincter contractions impairing storage and/or voiding. Conservative treatments managing neurogenic bladder post-injury, such as oral pharmacotherapy and catheterization, are important components of urological surveillance and clinical care. However, as urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments. Several human and animal studies, including our previously published reports, have documented gains in bladder function due to activity-based recovery strategies, such as locomotor training. Furthermore, epidural stimulation of the spinal cord (scES) combined with intense activity-based recovery training has been shown to produce volitional lower extremity movement, standing, as well as improve the regulation of cardiovascular function. In our center, several participants anecdotally reported improvements in bladder function as a result of training with epidural stimulation configured for motor systems. Thus, in this study, the effects of activity-based recovery training in combination with scES were tested on bladder function, resulting in improvements in overall bladder storage parameters relative to a control cohort (no intervention). However, elevated blood pressure elicited during bladder distention, characteristic of autonomic dysreflexia, was not attenuated with training. We then examined, in a separate, large cross-sectional cohort, the interaction between detrusor pressure and blood pressure at maximum capacity, and found that the functional relationship between urinary bladder distention and blood pressure regulation is disrupted. Regardless of one’s bladder emptying method (indwelling suprapubic catheter vs. intermittent catheterization), autonomic instability can play a critical role in the ability to improve bladder storage, with SCI enhancing the vesico-vascular reflex. These results support the role of intersystem stimulation, integrating scES for both bladder and cardiovascular function to further improve bladder storage.

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Section: Discussionmentioning

confidence: 99%

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury

Herrity

Aslan

Ugiliweneza

et al. 2021

Front. Syst. Neurosci.

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“…Both gentamicin sulfate (GentaFuse; Henry Schein Animal Health, Dublin, OH) and meloxicam (Eloxiject; Henry Schein Animal Health) were injected subcutaneously per established post-operative care procedures. 10 , 22 , 23 Physiological saline was also administered post-operatively (5 mL before contusion and 5 mL after contusion). Bladder emptying by the Crede maneuver was performed three times daily until individual animals reached reflexive bladder function (by 6 days 24 , 25 ).…”

Section: Methodsmentioning

confidence: 99%

“…Our group has previously shown, using a pre-clinical animal incomplete contusion model, that 1) polyuria occurs regardless of severity of SCI, 6 2) alterations of hormones affecting diuresis are present at 14 days post-injury (dpi), 9 and 3) related receptor/channel densities are altered in the kidney at 10 weeks post-SCI. 10 Although several key hormones and their receptors in the kidney impacting fluid balance have been shown to contribute to the mechanisms underlying SCI-induced polyuria/nocturia, more information is needed for the optimization of therapeutic approaches. 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

“… 10 Although several key hormones and their receptors in the kidney impacting fluid balance have been shown to contribute to the mechanisms underlying SCI-induced polyuria/nocturia, more information is needed for the optimization of therapeutic approaches. 9 , 10 …”

Section: Introductionmentioning

confidence: 99%

“… 9–11 We have also shown that kidney aquaporin-2 (AQP2) channels and epithelial sodium channels (ENaCs) were significantly decreased post-SCI in adult male rats. 10 Together, these fluctuations in AVP and ANP and their accompanying receptors/channels lead to an increase in urine production based on their physiological function. These receptors also play major roles in salt and fluid balance within the body, as well as cardiovascular homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Timeline of Changes in Biomarkers Associated with Spinal Cord Injury–Induced Polyuria

Gumbel

Yang

Hubscher

2021

Neurotrauma Reports

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Deficits in upper and lower urinary tract function, which include detrusor overactivity, urinary incontinence, detrusor-sphincter dyssynergia, and polyuria, are among the leading issues that arise after spinal cord injury (SCI) affecting quality of life. Given that overproduction of urine (polyuria) has been shown to be associated with an imbalance in key regulators of body fluid homeostasis, the current study examined the timing of changes in levels of various relevant hormones, peptides, receptors, and channels post-contusion injury in adult male Wistar rats. The results show significant up- or downregulation at various time points, beginning at 7 days post-injury, in levels of urinary atrial natriuretic peptide, serum arginine vasopressin (AVP), kidney natriuretic peptide receptor-A, kidney vasopressin-2 receptor, kidney aquaporin-2 channels, and kidney epithelial sodium channels (β- and γ-, but not α-, subunits). The number of AVP-labeled neurons in the hypothalamus (supraoptic and -chiasmatic, but not paraventricular, nuclei) was also significantly altered at one or more time points. These data show significant fluctuations in key biomarkers involved in body fluid homeostasis during the post-SCI secondary injury phase, suggesting that therapeutic interventions (e.g., desmopressin, a synthetic analogue of AVP) should be considered early post-SCI.

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Hormonal events and spinal cord injury: A focus on vasopressin and natriuretic peptide

Gumbel

Hubscher

2022

Cellular, Molecular, Physiological, and Behavioral Aspects of Spinal Cord Injury

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Activity-Based Training Reverses Spinal Cord Injury-Induced Changes in Kidney Receptor Densities and Membrane Proteins

Cited by 7 publications

References 65 publications

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury

Improvements in Bladder Function Following Activity-Based Recovery Training With Epidural Stimulation After Chronic Spinal Cord Injury

Timeline of Changes in Biomarkers Associated with Spinal Cord Injury–Induced Polyuria

Hormonal events and spinal cord injury: A focus on vasopressin and natriuretic peptide

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