Early interventions to prevent lower urinary tract dysfunction after spinal cord injury: a systematic review.

STUDY DESIGN: Systematic review. OBJECTIVES: To synthetise the available scientific literature reporting early interventions to prevent neurogenic lower urinary tract dysfunction (NLUTD) after acute supra-sacral spinal cord injury (SCI). METHODS: The present systematic review is reported according to the PRISMA guidelines and identified articles published through April 2021 in the PubMed, Embase, ScienceDirect and Scopus databases with terms for early interventions to prevent NLUTD after SCI. Abstract and full-text screenings were performed by three reviewers independently, while two reviewers performed data extraction independently. An article was considered relevant if it assessed: an in-vivo model of supra-sacral SCI, including a group undergoing an early intervention compared with at least one control group, and reporting clinical, urodynamic, biological and/or histological data. RESULTS: Of the 30 studies included in the final synthesis, 9 focused on neurotransmission, 2 on the inflammatory response, 10 on neurotrophicity, 9 on electrical nerve modulation and 1 on multi-system neuroprosthetic training. Overall, 29/30 studies reported significant improvement in urodynamic parameters, for both the storage and the voiding phase. These findings were often associated with substantial modifications at the bladder and spinal cord level, including up/downregulation of neurotransmitters and receptors expression, neural proliferation or axonal sprouting and a reduction of inflammatory response and apoptosis. CONCLUSIONS: The present review supports the concept of early interventions to prevent NLUTD after supra-sacral SCI, allowing for the emergence of a potential preventive approach in the coming decades.

Acute, severe traumatic spinal cord injury: improving urinary bladder function by optimizing spinal cord perfusion.

OBJECTIVE: The authors sought to investigate the effect of acute, severe traumatic spinal cord injury on the urinary bladder and the hypothesis that increasing the spinal cord perfusion pressure improves bladder function. METHODS: In 13 adults with traumatic spinal cord injury (American Spinal Injury Association Impairment Scale grades A-C), a pressure probe and a microdialysis catheter were placed intradurally at the injury site. We varied the spinal cord perfusion pressure and performed filling cystometry. Patients were followed up for 12 months on average. RESULTS: The 13 patients had 63 fill cycles; 38 cycles had unfavorable urodynamics, i.e., dangerously low compliance (< 20 mL/cmH2O), detrusor overactivity, or dangerously high end-fill pressure (> 40 cmH2O). Unfavorable urodynamics correlated with periods of injury site hypoperfusion (spinal cord perfusion pressure < 60 mm Hg), hyperperfusion (spinal cord perfusion pressure > 100 mm Hg), tissue glucose < 3 mM, and tissue lactate to pyruvate ratio > 30. Increasing spinal cord perfusion pressure from 67.0 ± 2.3 mm Hg (average ± SE) to 92.1 ± 3.0 mm Hg significantly reduced, from 534 to 365 mL, the median bladder volume at which the desire to void was first experienced. All patients with dangerously low average initial bladder compliance (< 20 mL/cmH2O) maintained low compliance at follow-up, whereas all patients with high average initial bladder compliance (> 100 mL/cmH2O) maintained high compliance at follow-up. CONCLUSIONS: We conclude that unfavorable urodynamics develop within days of traumatic spinal cord injury, thus challenging the prevailing notion that the detrusor is initially acontractile. Urodynamic studies performed acutely identify patients with dangerously low bladder compliance likely to benefit from early intervention. At this early stage, bladder function is dynamic and is influenced by fluctuations in the physiology and metabolism at the injury site; therefore, optimizing spinal cord perfusion is likely to improve urological outcome in patients with acute severe traumatic spinal cord injury.

Urologic guidelines for the care and management of people with spina bifida.

PURPOSE: The life expectancy for people with spina bifida has increased, thus resulting in greater need for guidelines in urologic care in order to protect normal renal function, to develop strategies for urinary continence, and to advance independence through adult years. METHODS: The English literature was assessed from 2002-2015; greater than 300 publications identified. Case reports and opinion pieces were eliminated leaving 100 for in depth review. Clinical questions were then established for each age group that allowed for focused assessment. RESULTS: There was no Level 1 evidence for any of the defined clinical questions. This resulted in group consensus for all questions throughout all age groups. Guidelines were provided for identifying a symptomatic urinary infection, the role of urodynamic bladder testing and identification of bladder hostility, determining methods of renal function assessment and surveillance, the initiation of continence control, and transitioning to self-care through the teen and adult years. CONCLUSION: Urologic guidelines continue to be based on clinical consensus due to the lack of high level evidence-based research. Further research is required in all aspects of urologic management. While not the "Standard of Care," these guidelines should be considered "Best Practice".

Update from TASCI, a Nationwide, Randomized, Sham-controlled, Double-blind Clinical Trial on Transcutaneous Tibial Nerve Stimulation in Patients with Acute Spinal Cord Injury to Prevent Neurogenic Detrusor Overactivity.

Transcutaneous tibial nerve stimulation has the potential to revolutionize the management of lower urinary tract dysfunction in patients with acute spinal cord injury. TASCI is a nationwide randomized, sham-controlled, double-blind clinical trial for which the preparatory phase has been successfully completed.

[Original strategy for prevention of recurrent symptomatic urinary tract infections in patients with neurogenic bladder: Bacterial interference, state of the art]. / Stratégie préventive originale des infections urinaires symptomatiques chez les patients porteurs d'une vessie neurologique : l'interférence bactérienne, état de l'art.

PURPOSE: Urinary tract infection (UTI) is the most common complication in patients with neurogenic bladder. The long-term use of antibiotic drugs induces an increase in antimicrobial resistance and adverse drug reactions. Bacterial interference is a new concept to prevent recurrent UTI which consists in a bladder colonization with low virulence bacteria. We performed a literature review on this emerging therapy. MATERIALS AND METHODS: Literature review of bacterial interference to prevent symptomatic urinary tract infection in neurological population. RESULTS: Seven prospectives study including 3 randomized, double-blind and placebo controlled trial were analyzed. The neurological population was spinal cord injured in most cases. The bladder colonization was performed with 2 non-pathogen strains of Escherichia coli: HU 2117 and 83972. At 1 month, 38 to 83% of patients were colonized. Mean duration of colonization was 48.5 days to 12.3 months. All studies showed that colonization might reduce the number of urinary tract infections and is safe with absence of serious side effects. CONCLUSION: Bacterial interference is a promising alternative therapy for the prevention of recurrent symptomatic urinary tract infections in neurogenic patients. This therapy should have developments for a daily use practice and for a long-term efficacy.

Detrusor Acontractility after Acute Spinal Cord Injury-Myth or Reality?

PURPOSE: We assessed urodynamic parameters within the first 40 days after spinal cord injury to investigate whether the detrusor is acontractile during the acute phase of spinal cord injury. MATERIALS AND METHODS: We performed a prospective cohort study in 54 patients with neurogenic lower urinary tract dysfunction due to acute spinal cord injury who underwent urodynamic investigation within the first 40 days after injury at a single university spinal cord injury center. RESULTS: Urodynamic investigation revealed an acontractile detrusor in only 20 of the 54 patients (37%) but unfavorable urodynamic parameters in 34 (63%). We found detrusor overactivity in 32 patients, detrusor-sphincter dyssynergia in 25, maximum storage detrusor pressure greater than 40 cm H2O in 17, vesicoureteral reflux in 3 and low bladder compliance (less than 20 ml/cm H2O) in 1. More than 1 unfavorable urodynamic parameter per patient was possible. CONCLUSIONS: In contrast to the common notion of an acontractile detrusor during acute spinal cord injury, almost two-thirds of our patients showed unfavorable urodynamic parameters within the first 40 days after spinal cord injury. Considering that early treatment of neurogenic lower urinary tract dysfunction in patients with acute spinal cord injury might improve the long-term urological outcome, urodynamic investigation should be performed timely to optimize patient tailored therapy.

Current concepts and practical techniques of nerve-sparing laparoscopic radical hysterectomy.

Laparoscopic radical hysterectomy has been widely performed for patients with early-stage cervical cancer. The operative techniques for nerve-sparing to avoid bladder dysfunction have been established during the past three decades in abdominal radical hysterectomy, but how these techniques can be applied to laparoscopic surgery has not been fully discussed. Prolonged operation time or decreased radicality due to less accessibility via a limited number of trocars may be a disadvantage of the laparoscopic approach, but the magnified visual field in laparoscopy may enable fine manipulation, especially for preserving autonomic nerve tracts. The present review article introduces the practical techniques for sparing bladder branches of pelvic nerves in laparoscopic radical hysterectomy based on understanding of the pelvic anatomy, clearly focusing on the differences from the techniques in abdominal hysterectomy.

Intravesical TRPV4 blockade reduces repeated variate stress-induced bladder dysfunction by increasing bladder capacity and decreasing voiding frequency in male rats.

Individuals with functional lower urinary tract disorders including interstitial cystitis (IC)/bladder pain syndrome (BPS) and overactive bladder (OAB) often report symptom (e.g., urinary frequency) worsening due to stress. One member of the transient receptor potential ion channel vanilloid family, TRPV4, has recently been implicated in urinary bladder dysfunction disorders including OAB and IC/BPS. These studies address the role of TRPV4 in stress-induced bladder dysfunction using an animal model of stress in male rats. To induce stress, rats were exposed to 7 days of repeated variate stress (RVS). Quantitative PCR data demonstrated significant (P ≤ 0.01) increases in TRPV4 transcript levels in urothelium but not detrusor smooth muscle. Western blot analyses of split urinary bladders (i.e., urothelium and detrusor) showed significant (P ≤ 0.01) increases in TRPV4 protein expression levels in urothelial tissues but not detrusor smooth muscle. We previously showed that RVS produces bladder dysfunction characterized by decreased bladder capacity and increased voiding frequency. The functional role of TRPV4 in RVS-induced bladder dysfunction was evaluated using continuous, open outlet intravesical infusion of saline in conjunction with administration of a TRPV4 agonist, GSK1016790A (3 µM), a TRPV4 antagonist, HC067047 (1 µM), or vehicle (0.1% DMSO in saline) in control and RVS-treated rats. Bladder capacity, void volume, and intercontraction interval significantly decreased following intravesical instillation of GSK1016790A in control rats and significantly (P ≤ 0.01) increased following administration of HC067047 in RVS-treated rats. These results demonstrate increased TRPV4 expression in the urothelium following RVS and that TRPV4 blockade ameliorates RVS-induced bladder dysfunction consistent with the role of TRPV4 as a promising target for bladder function disorders.

[Urethral condyloma in a patient with neurogenic bladder dysfunction: a therapeutic challenge]. / Urethrale Kondylome bei einem Patienten mit neurogener Blasenfunktionsstörung : Eine therapeutische Herausforderung.

Urethral condyloma is a therapeutic challenge. This article reports the case of a patient with spinal cord injury with the incidental finding of a massive spread of urethral condyloma. After removal of the condyloma with biopsy forceps neither recurrence of the condyloma nor a urethral stricture occurred. In patients where intermittent catheterization is performed, condyloma may be dispersed into the bladder, therefore, prompt endoscopic removal is crucial. As condyloma frequently recurs even after complete removal regular controls are mandatory.

[The future of invasive neuromodulation: new techniques and expanded indications]. / Die Zukunft der invasiven Neuromodulation : Neue Techniken und erweiterte Indikationen.

Due to the increasing popularity of neuromodulation, the number of indications and patient groups to which this technique is offered is also increasing. We evaluated the currently available data concerning neuromodulation in geriatric patients, children and patients with spinal cord injury and potential alternatives regarding neural targets and implantation techniques.The evidence of the use of neuromodulation in these patient groups is low. In geriatric patients, the use of neuromodulation seems to be justified. The few existing results concerning neuromulation in children are positive; however, there are no data about long term effects of neuromodulation on the growing organism. In patients with spinal cord injury, neuromodulation by microsurgical nerve anastomosis does not seem to be successful. According to the preliminary data of a single study, neuromodulation in acute spinal cord injury may prevent development of a neurogenic bladder dysfunction. The laparoscopic implantation of electrodes for neuromodulation unfolds new technical opportunities; however, until today there is no proof of the efficacy of this technique. Pudendal neuromodulation appears to be a meaningful addition to the therapeutic armamentarium for selected indications.The existing studies demonstrate the future opportunities of neuromodulation also in geriatric patients, children and patientens with spinal cord injuries. However, especially in the latter two groups, further studies concerning effectiveness and long term consequences are mandatory prior to offering these techniques to patients in everyday practise.

Determining outcomes, adverse events, and predictors of success after sacral neuromodulation for lower urinary disorders in women.

INTRODUCTION AND HYPOTHESIS: The objective of this study was to determine the predictors of successful treatment of lower urinary tract disorders with sacral nerve stimulation (SNS) and the rate of adverse events and reoperations. METHODS: A retrospective case series of patients who underwent SNS at a single institution was analyzed. RESULTS: Seventy-six patients underwent stage I trial of SNS. Fifty-eight (76%) patients experienced improvement and underwent placement of an implantable pulse generator with a mean follow-up of 23.7 months (SD ± 22.3). Surgical revisions occurred in 14/58 (24%) patients and 15/58 (26%) patients had the device explanted after a mean of 2.8 years (SD ± 1.7). Patients with greater than ten incontinence episodes per day were more likely to have a successful stage I trial compared to those with less than five (OR = 10.3; 95% CI 2.1 to 50.60). CONCLUSIONS: Although SNS is a safe and effective therapy for lower urinary tract disorders, it is associated with a high reoperation rate.

The measurement of vesical detrusor electromyographic activity during nerve-sparing radical hysterectomy.

OBJECTIVE: To evaluate the feasibility for confirming the preservation of the parasymphathetic nerve pathway innervating the bladder during nerve-sparing radical hysterectomy (RH). METHODS: A total of 20 patients underwent nerve-sparing RH. Intraoperative electrical stimulation (IES) were performed on the root of pelvic splanchnic nerve (PSN) trunk while recording the electromyographic (EMG) activity of the vesical detrusor. The average duration achieving residual urine ≤50 mL and urodynamic study (UDS) was observed. RESULTS: Evoked potentials were recorded when stimulating, in 18 patients who were referred IES-positive. Its duration was 9.89 days. The UDS results indicated that all voided normally. The remaining 2 IES-negative cases with no evoked potentials had longer duration and the micturitions were performed using abdominal pressure. CONCLUSION: During nerve-sparing RH, IES based on the measurement of EMG activity is a useful tool for confirmation of the preservation of parasymphathetic nerve pathway innervating the bladder and prediction of the postoperative bladder function.

The M2-muscarinic receptor inhibits the development of streptozotocin-induced neuropathy in mouse urinary bladder.

We investigate the role of M(2)-muscarinic receptors in maintaining neurogenic bladder contraction during hyperglycemia. Mice were injected with a single dose of streptozotocin (125 mg/kg), and neurogenic contraction of urinary bladder from wild type and M(2)-muscarinic receptor knockout (M(2) KO) mice was measured at 8 to 24 weeks after treatment. In wild-type bladder lacking urothelium, the summation of the cholinergic (64%) and purinergic (56%) components of the electrical-field-stimulated response exceeded 100%, indicating a reserve capacity. Although the cholinergic component was slightly less in the M(2) KO mouse, the total electrical-field-stimulated contraction was the same as wild type. The cholinergic and purinergic components of contraction in wild-type bladder were minimally affected by streptozotocin treatment. In M(2) KO bladder, streptozotocin treatment reduced both the cholinergic (after 8-9 and 20-24 weeks) and purinergic (after 20-24 weeks only) components. The loss of function was approximately 50 to 70%. Similar results were observed in bladder with intact urothelium. M(2) KO bladder was more sensitive to the relaxant effect of isoproterenol compared with wild type, and this difference significantly increased at the early and late time points after streptozotocin treatment. In the presence of urothelium, however, this difference in isoproterenol sensitivity was smaller with streptozotocin treatment, but this trend reversed over time. Our results show that M(2) receptors oppose urinary bladder distension in wild-type bladder and inhibit streptozotocin-induced neuropathy.

Effect of nerve-sparing radical hysterectomy on bladder function recovery and quality of life in patients with cervical carcinoma.

OBJECTIVE: To investigate the bladder function recovery and quality of life (QOL) using nerve-sparing radical hysterectomy (NSRH) in treating early invasive cervical carcinoma. METHODS: Subjects included patients who underwent radical hysterectomy by laparotomy for early-stage cervical carcinoma. Thirty-one patients were randomly assigned to 2 groups: group A, 15 patients who underwent NSRH; and group B, 16 patients who underwent classical radical hysterectomy. We observed the patients' general clinical information, surgical characteristics, postoperative vital signs, pathological findings, adjuvant therapies, and adverse effects. A urodynamic study was used to assess the bladder function. The patients' QOL was evaluated by Functional Assessment of Cervical Cancer Therapy (FACT-Cx). RESULTS: Twenty-nine patients completed the study. No significant differences were found in age, body mass index, surgery characteristics, pathological findings, adjuvant therapies, and main adverse effects between the 2 groups (P > 0.05). The postoperative time of bladder function recovery in group A was obviously earlier than that in group B (P < 0.05). The urodynamic study showed that the extent of bladder function recovery in group A was better than that in group B (P < 0.05). The QOL in group A evaluated 1 year after operation was improved compared with that in group B (P < 0.05). The QOL analysis showed that group A did much better than group B in social and family life, emotional well-being, working status, and the symptom correlated with the operation (P < 0.05). No significant differences were found in basic bodily functions (P > 0.05). CONCLUSIONS: Nerve-sparing radical hysterectomy is a safe and reliable technique for early invasive cervical carcinoma. The postoperative bladder function recovery and the patients' QOL were improved after NSRH compared with the control group. Therefore, NSRH could be an alternative management to modify the classical surgery for cervical carcinoma with International Federation of Gynecology and Obstetrics stages IB1 to IIA.

The encrustation and blockage of long-term indwelling bladder catheters: a way forward in prevention and control.

OBJECTIVES: To review the literature showing that understanding how Foley catheters become encrusted and blocked by crystalline bacterial biofilms has led to strategies for the control of this complication in the care of patients undergoing long-term indwelling bladder catheterization. METHODS: A comprehensive PubMed search of the literature published between 1980 and December 2009 was made for relevant articles using the Medical Subject Heading terms 'biofilms', 'urinary catheterization', 'catheter-associated urinary tract infection' and 'urolithiasis'. Papers on catheter-associated urinary tract infections and bacterial biofilms collected during 40 years of working in the field were also reviewed. RESULTS: There is strong experimental and epidemiological evidence that infection by Proteus mirabilis is the main cause of the crystalline biofilms that encrust and block Foley catheters. The ability of P. mirabilis to generate alkaline urine and to colonize all available types of indwelling catheters allows it to take up stable residence in the catheterized tract in bladder stones and cause recurrent catheter blockage. CONCLUSION: The elimination of P. mirabilis by antibiotic therapy as soon as it appears in the catheterized urinary tract could improve the quality of life for many patients and reduce the current expenditure of resources when managing the complications of catheter encrustation and blockage. For patients who are already chronic blockers and stone formers, antibiotic treatment is unlikely to be effective owing to the resistance of cells in the crystalline biofilms. Strategies such as increasing fluid intake with citrated drinks could control the problem until bladder stone removal can be organized.

Diabetic bladder dysfunction: current translational knowledge.

PURPOSE: Diabetes mellitus, a metabolic disorder caused by an absolute or relative deficiency of insulin, is a debilitating and costly disease with multiple serious complications. Lower urinary tract complications are among the most common complications of diabetes mellitus. The most common, bothersome lower urinary tract complication of diabetes mellitus is diabetic cystopathy or diabetic bladder dysfunction. We reviewed the current translational knowledge of diabetic bladder dysfunction. MATERIALS AND METHODS: We performed a search of the English literature through PubMed. The key words used were diabetes and bladder dysfunction or cystopathy. Our data and perspective are provided for consideration of the future direction of research. RESULTS: Despite traditional recognition of diabetic bladder dysfunction as a voiding problem characterized by poor emptying and overflow incontinence, recent clinical and experimental evidence indicate storage problems such as urgency and urge incontinence in diabetes mellitus cases. Recent experimental evidence from studies of diabetic bladder dysfunction in small animal models of diabetes mellitus show a temporal effect on diabetic bladder dysfunction. Early phase diabetes mellitus causes compensated bladder function and the late phase causes decompensated bladder function. The temporal theory could plausibly provide the scientific road map to correlate clinical and experimental findings, and identify the role of mechanisms such as polyuria, hyperglycemia, oxidative stress, autonomic neuropathy and decompensation of the bladder contractile apparatus in the creation of clinical and experimental manifestations of diabetic bladder dysfunction. CONCLUSIONS: Diabetic bladder dysfunction includes time dependent manifestations of storage and emptying problems. Identifying mechanistic pathways would lead to the identification of therapeutic intervention.

Clean intermittent catheterization: educational booklet directed to caregivers of children with neurogenic bladder dysfunction.

PURPOSE: The purpose of this study was to propose a systematic teaching and learning strategy for Brazilian caregivers of children with neurogenic bladder dysfunction(NBD), by using an illustrated booklet written in Portuguese. DESIGN: Descriptive study. SUBJECTS AND SETTING: Caregivers of children requiring clean intermittent catheterization (CIC) were approached when attending the pediatric urology outpatient clinic of Hospital de Base in Sao Jose do Rio Preto city, Brazil. METHODS: After educational sessions, a supervised procedure was done, with the child's caregiver observing the technique. RESULTS: Twenty-three caregivers of children with NBD provided feedback on a CIC teaching booklet. The children were all cared for at the pediatric urology outpatient clinic of a teaching hospital in Sao Jose do Rio Preto city, Brazil. The booklet was evaluated as "excellent" concerning organization and the quality of the illustrations by the majority of the caregivers. All caregivers stated that they had developed the ability to perform CIC successfully; 61% evaluated their learning process as "excellent," whereas 39% evaluated it as "good." CONCLUSION: The booklet successfully reached the goals and now is implemented in orientations about CIC.

Spinal myxopapillary ependymoma: neurological deterioration in patients treated with surgery.

STUDY DESIGN: A retrospective multicenter study of series of 20 patients with myxopapillary ependymomas, which underwent surgery. OBJECTIVE.: To evaluate the postoperative outcomes of patients surgically treated for spinal myxopapillary ependymoma. Neurologic deterioration after tumor resection is discussed in terms of the tumor encapsulation. SUMMARY OF BACKGROUND DATA.: Myxopapillary ependymomas occur most commonly in the cauda equina and/or conus medullaris region. Most series published in the literature have covered postoperative tumor recurrence and role of adjuvant radiotherapy. Few contradistinctive studies in postoperative neurological deficit were reviewed from the standpoints of MRI and histopathologic findings. METHODS: A total of 20 patients were recruited and charts, MRI, intraoperative findings, and pathologic findings were reviewed. The follow-up period ranged from 2 to 12 years (median, 72.9 months). The surgical procedures were defined as gross total removal, piecemeal total removal, and subtotal removal. Postoperative radiotherapy was given in 3 patients in whom removal had been subtotal. RESULTS: Gross total removal was achieved in 14 patients, piecemeal gross total and subtotal removal in 3 patients each. Neurologic deterioration after surgery was seen in 5 patients, all of which were unencapsulated tumors consisting of piecemeal gross total removal in 2 patients and subtotal removal in 3 patients. Recovery of postoperative bladder dysfunction remained unchanged in 2 patients. There were no tumor recurrence and progression of the remaining tumors. Unencapsulated tumors were more frequently seen in heterogeneously enhanced tumors on MRI than in homogenously enhanced tumors with significant difference. CONCLUSION: In the unencapsulated ependymomas, tumor separation and manipulation of the surrounding neural tissue caused neurologic injury. The heterogeneously enhanced ependymoma not only should be evaluated and treated meticulously, but also surgeons should not stick to total removal in infiltrated and adhering tumors as subtotally resected tumors with postoperative radiotherapy have not always recurred.

Transplantation and repair: combined cell implantation and chondroitinase delivery prevents deterioration of bladder function in rats with complete spinal cord injury.

STUDY DESIGN: Additional examination. In this study, we report changes in bladder function after a combined treatment that was designed to study axonal regeneration after complete spinal cord injury (SCI) in rats. OBJECTIVES: To report effects on bladder function following the administration of a combined treatment for complete SCI. SETTING: University of Alberta, Faculty of Rehabilitation Medicine, Edmonton, Canada. METHODS: Eight rats received Schwann cells in Matrigel-filled guidance channels, olfactory ensheathing glia and chondroitinase ABC at the lesion site following complete thoracic SCI. Controls (n=7) received Matrigel only. Daily bladder examinations were performed. Analysis of bladder size, wall thickness, actin and collagen type III was performed after 14 weeks. RESULTS: Following SCI, both groups regained bladder voiding after 3 weeks. However, 2 weeks later, incontinence was observed in all untreated rats and two treated rats. Post-mortem examination of bladders revealed enlarged bladder sizes. Thicker bladder walls were found in untreated rats, which were composed of disorganized bundles of smooth muscle fibers surrounded by high amounts of collagen (type III). CONCLUSION: We show that the combined treatment prevents collagen deposition in bladder walls and maintains the rat's ability to void efficiently. Although the mechanism responsible for this improvement is unclear, our study shows that the present combinatory therapy can influence bladder function, thus expanding their utility as a broad reparative approach for SCI.