Choice of cystometric technique impacts detrusor contractile dynamics in wistar rats

Medina-Aguiñaga, Daniel; Hoey, Robert F.; Muñoz, Alvaro; Altamira‐Camacho, Moises; Quintanar, J. Luis; Hubscher, Charles H.

doi:10.14814/phy2.14724

Cited by 6 publications

(9 citation statements)

References 63 publications

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“…2 E). This bursting pattern of EUS activity found in sham animals is characteristic of that found in spinally intact animals in the literature, including our previously published reports 23 , 24 . For shams, the mean voided volume was 0.53 ± 0.06 ml, ICI duration 109.1 ± 40.9 s, in–out ratio 0.98 ± 0.22 and, 3.2 ± 0.33 s burst duration (Supplemental Table 1 ).…”

Section: Resultssupporting

confidence: 82%

“…3 C) occurred during L3 scES. Previous data also shows that a higher in/out ratio is a consequence of longer EUS bursting periods 23 . The frequency dependent increase of the in–out ratio in this study is consistent with those observations (Fig.…”

Section: Discussionmentioning

confidence: 86%

“…Thus, targeting these circuitries with a therapeutic intervention such as scES would require some degree of initial mapping to optimize functional outcomes across individuals. Furthermore, the surgical placement of the bladder catheter and/or EUS electrodes, could also impact urodynamic performance in SCI animals 23 , 41 .…”

Section: Discussionmentioning

confidence: 99%

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Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats

Medina-Aguiñaga

Hoey

Wilkins

et al. 2023

Sci Rep

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Recent pre-clinical and clinical spinal cord epidural stimulation (scES) experiments specifically targeting the thoracolumbar and lumbosacral circuitries mediating lower urinary tract (LUT) function have shown improvements in storage, detrusor pressure, and emptying. With the existence of a lumbar spinal coordinating center in rats that is involved with external urethral sphincter (EUS) functionality during micturition, the mid-lumbar spinal cord (specifically L3) was targeted in the current study with scES to determine if the EUS and thus the void pattern could be modulated, using both intact and chronic complete spinal cord injured female rats under urethane anesthesia. L3 scES at select frequencies and intensities of stimulation produced a reduction in void volumes and EUS burst duration in intact rats. After chronic transection, three different subgroups of LUT dysfunction were identified and the response to L3 scES promoted different cystometry outcomes, including changes in EUS bursting. The current findings suggest that scES at the L3 level can generate functional neuromodulation of both the urinary bladder and the EUS in intact and SCI rats to enhance voiding in a variety of clinical scenarios.

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Section: Resultssupporting

confidence: 82%

Section: Discussionmentioning

confidence: 86%

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Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats

Medina-Aguiñaga

Hoey

Wilkins

et al. 2023

Sci Rep

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“…As further support for the results obtained with the behavioral evaluations, we performed cystometric 22 and electromyographic evaluations of the external urethral sphincter 18 in rats from all groups. It is complicated to compare these results with previous studies using, for instance, a contusion SCI model, 23 nonetheless we found no differences for the duration of IPHFO, voiding volumes, threshold pressure or amplitude of the electromyographic response among the four groups, although the SCI‐BoNT/A rats show a trend towards improved CMG/EMG parameters.…”

Section: Discussionmentioning

confidence: 63%

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site

Gandara,

Palacios,

Luis Quintanar

et al. 2023

Neurourology and Urodynamics

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ObjectiveTo assess the effect of an injection of botulinum toxin A (BoNT/A) at the epicenter of the spinal cord injury (SCI) site on the recovery of lower urinary tract function in female rats with thoracic SCI.Materials and MethodsTwenty‐four female Wistar rats with Sham (laminectomy at T8/T9 level) or SCI (at T8/T9; 30 g compression for 5 s) were assigned into Sham‐SS (injected with 5 µL of saline solution), Sham‐BoNT/A (injected with 15 pg/rat, equivalent to 7.5 Units/kg of BoNT/A in 5 µL volume), SCI‐SS (injured and injected with saline), SCI‐BoNT/A (injured and injected with BoNT/A), N = 6 per group. Weekly evaluation of stereotyped micturition behavior, hind‐limb nociception, and locomotor activity was performed 1 week before and during 6 weeks after surgery. Subsequently, all groups underwent simultaneous electromyography of the external urethral sphincter (EUS‐EMG) and cystometric (CMG) studies.ResultsA compression SCI at the T8/T9 thoracic level significantly impairs sensory and locomotive functions, as well as stereotyped micturition behavior. However, these impairments were improved by BoNT/A injection after SCI. Neither injections of saline solution nor BoNT/A had an appreciable effect on the same parameters evaluated in the Sham groups. The combined EUS‐EMG and CMG evaluations revealed important improvements of lower urinary tract physiology, particularly a reduction in the frequency of non‐voiding contractions and the properties of EUS bursting activity indicated as the amplitude of the EUS‐EMG signal and duration of burst electrical activity during effective voiding.ConclusionThe severe impairments on sensory and locomotive functions as well stereotyped micturition caused by an SCI could be potentially attenuated by an injection of a small amount of BoNT/A directly into the epicenter of the SCI region. A reduction in the release of neurotoxic neurotransmitters requiring the SNARE complex may be the mechanism triggered by BoNT/A to reduce neurotoxicity and hyperexcitability created in the SCI area to improve the survival of spinal cord cells involved in micturition.

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“…The variability of these results was very large and may also be explained in part by disturbances in the detrusor caused by the implantation of the catheter. 15 , 26 …”

Section: Discussionmentioning

confidence: 99%

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats

Sartori

Salemi

Hofer

et al. 2022

Neurotrauma Reports

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Despite the fact that a majority of patients with an injury to the spinal cord develop lower urinary tract dysfunction, only few treatment options are available currently once the dysfunction arises. Tibial nerve stimulation has been used in pilot clinical trials, with some promising results. Hence, we investigated whether the early application of transcutaneous tibial nerve stimulation in the animal model of spinal cord injured rats can prevent the development of detrusor overactivity and/or detrusor-sphincter-dyssynergia. Rats were implanted with a bladder catheter and external urethral sphincter electromyography electrodes. A dorsal over-hemisection, resulting in an incomplete spinal cord injury at the T8/9 spinal level, induced immediate bladder paralysis. One week later, the animals received daily tibial nerve or sham stimulation for 15 days. Effects of stimulation on the lower urinary tract function were assessed by urodynamic investigation. Measurements showed improvements of several key parameters of lower urinary tract function—in particular, non-voiding bladder contractions and intravesical pressure—immediately after the completion of the stimulation period in the stimulated animals. These differences extinguished one week later, however. In the dorsal horn of the lumbosacral spinal cord, a small significant increase of the density of C-fiber afferents layers I-II was found in the stimulated animals at four weeks after spinal cord injury. Tibial nerve stimulation applied acutely after spinal cord injury in rats had an immediate beneficial effect on lower urinary tract dysfunction; however, the effect was transitory and did not last over time. To achieve more sustainable, longer lasting effects, further studies are needed looking into different stimulation protocols using optimized stimulation parameters, timing, and treatment schedules.

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Choice of cystometric technique impacts detrusor contractile dynamics in wistar rats

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 6 publications

References 63 publications

Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats

Mid-lumbar (L3) epidural stimulation effects on bladder and external urethral sphincter in non-injured and chronically transected urethane-anesthetized rats

Improvement of neurogenic urinary dysfunctions in female rats treated with an injection of botulinum toxin A at the epicenter of the spinal cord injured site

Early Transcutaneous Tibial Nerve Stimulation Acutely Improves Lower Urinary Tract Function in Spinal Cord Injured Rats

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