Early sacral neuromodulation ameliorates urinary bladder function and structure in complete spinal cord injury minipigs.

AIMS: To determine the effects of early sacral neuromodulation (SNM) and pudendal neuromodulation (PNM) on lower urinary tract (LUT) function, minipigs with complete spinal cord injury (cSCI) were analyzed. SNM and PNM have been proposed as therapeutic approaches to improve bladder function, for example after cSCI. However, further evidence on efficacy is required before these methods can become clinical practice. METHODS: Eleven adults, female Göttingen minipigs with cSCI at vertebral level T11-T12 were included: SNM (n = 4), PNM (n = 4), and SCI control (SCIC: n = 3). Tissue from six healthy minipigs was used for structural comparisons. Stimulation was started 1 week after cSCI. Awake urodynamics was performed on a weekly basis. After 16 weeks follow-up, samples from the urinary bladder were taken for analyses. RESULTS: SNM improved bladder function with better capacities and lower detrusor pressures at voiding and avoided the emergence of detrusor sphincter dyssynergia (DSD). PNM and untreated SCI minipigs had less favorable outcomes with either DSD or constant urinary retention. Structural results revealed SCI-typical fibrotic alterations in all cSCI minipigs. However, SNM showed a better-balanced distribution of smooth muscle to connective tissue with a trend towards the reduced progression of bladder wall scarring. CONCLUSION: Early SNM led to an avoidance of the emergence of DSD showing a more physiological bladder function during a 4 month follow-up period after cSCI. This study might pave the way for the clinical continuation of early SNM for the treatment of neurogenic LUT dysfunction after SCI.

Cystometric and External Urethral Sphincter Measurements in Awake Rats with Implanted Catheter and Electrodes Allowing for Repeated Measurements.

Lower urinary tract function is mainly assessed by means of cystometric bladder function analysis in rodents. Conventional cystometries are usually performed as terminal analysis under urethane anesthesia. It is well known that anesthetic drugs can influence bladder function. Hence, the aim of this technique is to perform cystometric measurements of the urinary bladder and external urethral sphincter in lightly restrained awake rats. For this purpose, a bladder catheter is implanted into the bladder dome. Subsequently, two electrodes are implanted bilateral to the external urethral sphincter and a ground electrode is sutured to a non-responsive skeletal muscle. The bladder catheter and the three electrodes are finally tunneled subcutaneously to the neck region and affixed to a harness. With this technique, the lower urinary tract can be measured at multiple time points in the same animal to assess lower urinary tract function. The main application of this technique is the follow-up of simultaneous urinary bladder and external urethral sphincter function in awake healthy rats and after induction of a disease or injury. Moreover, subsequent lower urinary tract monitoring can be performed during evaluation of the disease/injury and to monitor treatment efficacy.

A new technique for minimal invasive complete spinal cord injury in minipigs.

BACKGROUND: The aim of this study was to develop a minimal invasive complete spinal cord injury (SCI) minipig model for future research applications. The minipig is considered a translationally relevant model for SCI research. However, a standardized minimal invasive complete SCI model for pigs has not yet been established. METHODS: Adult Göttingen minipigs were anesthetized and placed in extended prone position. After initial computed tomography (CT) scan, the skin was incised, a needle placed in the epidural fatty tissue. Using the Seldinger technique, a guidewire and dilators were introduced to insert the balloon catheter to Th12. After confirmation of the level Th11/Th12, the balloon was inflated to 2 atm for 30 min. The severity of the lesion was followed by CT and by MRI, and by immunohistochemistry. Function was assessed at the motor and sensory level. RESULTS: Duration of procedure was about 60 min including the 30-min compression time. The balloon pressure of 2 atm was maintained without losses. The lesion site was clearly discernible and no intradural bleeding was observed by CT. Neurological assessments during the 4-month follow-up time showed consistent, predictable, and stable neurological deficits. Magnetic resonance imaging analyses at 6 h and 4 weeks post SCI with final immunohistochemical analyses of spinal cord tissue underlined the neurological outcomes and proved SCI completeness. CONCLUSIONS: We have established a new, minimal invasive, highly standardized, CT-guided spinal cord injury procedure for minipigs. All risks of the open surgery can be excluded using this technique. This CT-guided SC compression is an excellent technique as it avoids long surgery and extensive trauma and allows a feasible inter-animal comparison.

Structural Changes of the Urinary Bladder After Chronic Complete Spinal Cord Injury in Minipigs.

PURPOSE: The aim of this study was to determine the structural changes of the urinary bladder after chronic spinal cord injury (SCI) in minipigs with the primary focus on the analysis of urinary bladder wall proteins and their quantitative distribution. METHODS: Seven Göttingen minipigs (adult, female) underwent a complete spinal cord transection. Follow-up time was 4 months during which the bladder was drained by frequent single catheterisation and data from the bladder diary and daily urine strip test were collected. Samples from the urinary bladder were taken, fixed in 4% paraformaldehyde and stained for histological analyses. Bladder wall thickness, single tissue quantities/distributions, types I and III collagen, and elastin quantifications were performed. Comparisons to healthy urinary bladder tissue of age-matched minipigs were performed for statistical analyses. RESULTS: No urinary tract infections were observed in our SCI minipig collective during follow-up. A trend towards a reduction in bladder volumes and an increase in incontinence periods were seen. The bladder wall thickness significantly increased after chronic SCI. Furthermore, bladder wall composition was severely altered by a significant loss of smooth muscle tissue and a significant increase in connective tissue. Elastic fibres were reduced in number and altered in their structural appearance after SCI. Type I collagen was significantly increased, while type III collagen was significantly decreased after SCI. CONCLUSIONS: Chronic SCI highlighted that the urinary bladder wall undergoes fibrotic events with reduced contractile and elastic properties due to changes of the bladder wall protein composition. These changes show in detail how SCI severely influences the urinary bladder wall composition and depicts the similarities between minipigs and humans.