Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity

Dewulf, Karel; Weyne, Emmanuel; Gevaert, Thomas; Deruyver, Yves; Voets, Thomas; Ridder, Dirk De; Everaerts, Wouter; Albersen, Maarten

doi:10.1111/bju.14649

Cited by 15 publications

(23 citation statements)

References 33 publications

(73 reference statements)

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“…Such hypersensitivity has been earlier demonstrated in ewes after their first spontaneous delivery 21 . This phenomenon has also been described in the bladder after partial denervation of the detrusor muscle 22 …”

Section: Discussionsupporting

confidence: 55%

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Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

Callewaert

Cunha

Dewulf

et al. 2020

Neurourology and Urodynamics

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Background Although pelvic floor dysfunction (PFD) has a multifactorial etiology, pregnancy and childbirth are considered crucial events predisposing to urinary incontinence as well as pelvic organ prolapse, which are highly prevalent. Rats are the most frequently used animal model and pudendal nerve crush (PNC) and vaginal distension (VD) are often used to mimic vaginal delivery. Objective To document the time course of events after simulated vaginal delivery (SVD) on the urethral sphincter and the vaginal smooth muscle layer. Materials and Methods Virgin female Sprague‐Dawley rats were subjected to SVD (PNC + VD) or sham surgery and evaluated at 7, 14, 21, and 42 days after the injury. Urethral function was determined in vivo by microultrasound during cystometry and vaginal smooth muscle layer was harvested for in vitro pharmacologic investigation by isometric tension recording. Furthermore, vaginal and urethral samples were investigated by immunohistochemistry and real‐time quantitative polymerase chain reaction. Results Microultrasound showed no bursting of the urethral sphincter in the SVD group at 7 days with a functional recovery starting at 14 days, and normal bursting at 21 and 42 days. Vaginal smooth muscle showed higher sensitivity to carbachol at 14 and 21 days after injury; however, at 42 days, its sensitivity decreased when compared with sham. Conclusion SVD induces urethral dysfunction and a shift in vaginal smooth muscle contractile responses to carbachol.

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Section: Discussionsupporting

confidence: 55%

“…21 This phenomenon has also been described in the bladder after partial denervation of the detrusor muscle. 22 To our knowledge, muscarinic receptor 2 (M2) upregulation following trauma has not been previously described in vaginal tissue ( Figure 5). This observation may contribute to the hypersensitivity described above.…”

Section: Discussionmentioning

confidence: 83%

Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

Callewaert

Cunha

Dewulf

et al. 2020

Neurourology and Urodynamics

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“…In another detrusor underactivity animal model of bilateral pelvic nerve crush injury 58 , 59 , the surgical procedure was different from ours. We used the posterior approach, but they used the transperitoneal approach.…”

Section: Discussionmentioning

confidence: 76%

“…Noritoshi Sekido et al reported an animal model of underactive bladder using lumbar canal stenosis (LCS) 57 . Karel Dewulf et al represented the functional and molecular characteristics of a detrusor underactivity rat model using bilateral pelvic nerve crush injury 58 . However, what is the difference between us and what’s new about us: in Zheng’s model, rats exhibited not only detrusor underactivity but also severe lower limb paralysis.…”

Section: Discussionmentioning

confidence: 99%

Functional, morphological and molecular characteristics in a novel rat model of spinal sacral nerve injury-surgical approach, pathological process and clinical relevance

Wang

et al. 2022

Sci Rep

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Spinal sacral nerve injury represents one of the most serious conditions associated with many diseases such as sacral fracture, tethered cord syndrome and sacral canal tumor. Spinal sacral nerve injury could cause bladder denervation and detrusor underactivity. There is limited clinical experience resolving spinal sacral nerve injury associated detrusor underactivity patients, and thus the treatment options are also scarce. In this study, we established a spinal sacral nerve injury animal model for deeper understanding and further researching of this disease. Forty 8 w (week) old Sprague Dawley rats were included and equally divided into sham (n = 20) and crush group (n = 20). Bilateral spinal sacral nerves of rats were crushed in crush group, and sham group received same procedure without nerve crush. Comprehensive evaluations at three time points (1 w, 4 w and 6 w) were performed to comprehend the nature process of this disease. According to urodynamic test, ultrasonography and retrograde urography, we could demonstrate severe bladder dysfunction after spinal sacral nerve injury along the observation period compared with sham group. These functional changes were further reflected by histological examination (hematoxylin-eosin and Masson’s trichrome staining) of microstructure of nerves and bladders. Immunostaining of nerve/bladder revealed schwann cell death, axon degeneration and collagen remodeling of bladder. Polymerase Chain Reaction results revealed vigorous nerve inflammation and bladder fibrosis 1 week after injury and inflammation/fibrosis returned to normal at 4 w. The CatWalk gait analysis was performed and there was no obvious difference between two groups. In conclusion, we established a reliable and reproducible model for spinal sacral nerve injury, this model provided an approach to evaluate the treatment strategies and to understand the pathological process of spinal sacral nerve injuries. It allowed us to understand how nerve degeneration and bladder fibrosis changed following spinal sacral nerve injury and how recovery could be facilitated by therapeutic options for further research.

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“…The hypogastric and pelvic nerves travel through the MPG before reaching target tissues, such as the bladder and urethra 9 . There are several reports about the involvement of these nerves in lower urinary tract function 10‐12 …”

Section: Introductionmentioning

confidence: 99%

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

Maeda

Hotta

Shibayama

et al. 2021

Neurourology and Urodynamics

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Aims: To investigate the relationship between lower urinary tract function and the accessory nerve (ACN) arising from the major pelvic ganglion (MPG). Methods: Ten-week-old male Wistar/ST rats were randomly divided into eight groups according to the type of treatment (sham or bilateral accessory nerve injury [BACNI]) and the duration of observation (3 days, 1 week, 2 weeks, or 4 weeks: Sham-3d, Sham-1w, Sham-2w, Sham-4w, BACNI-3d, BACNI-1w, BACNI-2ws, and BACNI-4w. BACNI was induced in the following manner: the ACN was crushed for 1 min (2 mm away from the MPG) using reverse-action tweezers. The same procedure was performed on both sides. On the last day of each observation period, the bladder function was measured by awake cystometry, and histological evaluation was performed. Results: All rats in the Sham groups micturated normally. In the BACNI-3d and BACNI-1w groups, all rats showed symptoms of overflow urinary incontinence (OUI). This OUI improved gradually over time. The bladder's size in the BACNI group was significantly larger than that in the Sham group (p < .01). In addition, fibrosis was observed in the subserosa of the bladder of rats in BACNI groups. Conclusion: The BACNI model rats exhibited OUI, suggesting that ACN is involved in the lower urinary tract function. It might be possible that ACN controls the function of either the bladder, the urethra, or both.

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Functional and molecular characterisation of the bilateral pelvic nerve crush injury rat model for neurogenic detrusor underactivity

Cited by 15 publications

References 33 publications

Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

Simulated vaginal delivery causes transients vaginal smooth muscle hypersensitivity and urethral sphincter dysfunction

Functional, morphological and molecular characteristics in a novel rat model of spinal sacral nerve injury-surgical approach, pathological process and clinical relevance

Impairment of accessory nerves around major pelvic ganglion leading to overflow urinary incontinence in rats

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