Restore Bladder Function Research Articles

Bladder drainage methods for acute urinary retention due to benign prostatic hyperplasia: patient-preference analysis

Introduction. Currently, the classical management of acute urinary retention creates a certain discomfort for the patient and leads to explore alternative method of management, such as intermittent catheterization, including focusing on the patient opinions.Objective. To assess the preference of high-risk patients for acute urinary retention relative to bladder drainage in the occurrence of acute urinary retention.Materials & methods. A survey was conducted among 200 ambulatory male patients. All the participants were tested to assess their mental status and ability to perform self-intermittent catheterization before filling out the questionnaire. The questionnaire included questions about the preferred method of bladder drainage for acute urinary retention, as well as factors influencing the patient's choice of self-intermittent catheterization in case of non-recovery. After completing the questionnaire, all the patients were shown a video on self-catheterization and asked to re-take the questionnaire after watching it. This allowed evaluating the impact of the training video on patients' preferences and their confidence in performing self-catheterization.Results. Among the 200 patients, 151 (75.5 %) preferred intermittent catheterization, while 40 (25.5 %) chose an indwelling urinary catheter. Additionally, 152 (76 %) patients opted for intermittent catheterization until the planned surgery, and 48 (24 %) selected a suprapubic catheter. The main factors influencing the patient choice of intermittent catheterization were: the desire to restore bladder function faster (on the first or second day) in 96 (63.2 %) patients; unwillingness to stay in the hospital in 56 (36.8 %); the desire to return to work in 22 (14.5 %); avoiding the use of a suprapubic catheter in 51 (33.5 %). After watching the video, there was a statistically significant change in patients' assessments of their ability to perform self-intermittent catheterization (p < 0.001).Conclusion. The patient's choice of the intermittent catheterization is significantly influenced by the patient self-confidence in the ability to practice self-intermittent catheterization and the demonstration of the video tutorial. Due to the high efficiency and safety of intermittent catheterization, this method should be introduced into clinical practice based on the proposed algorithm.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Construction of tissue-engineered bladders using an artificial acellular nanocomposite scaffold loaded with stromal vascular fraction secretome

Tissue engineering approaches offer promising alternative strategies for reconstructing bladder tissue; however, the low retention of transplanted cells and the possible risk of rejection limit their therapeutic efficacy. Clinical applicability is further limited by the lack of suitable scaffold materials to support the needs of various cell types. In the present study, we developed an artificial nanoscaffold system consisting of stromal vascular fraction (SVF) secretome (Sec) loaded onto zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, which were then incorporated into bladder acellular matrix. This artificial acellular nanocomposite scaffold (ANS) can achieve gradient degradation and slowly release SVF-Sec to promote tissue regeneration. Furthermore, even after long-term cryopreservation, this completely acellular bladder nanoscaffold material still maintains its efficacy. In a rat bladder replacement model, ANS transplantation demonstrated potent proangiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function. Our study demonstrates the safety and efficacy of the ANS, which can play a stem cell-like role while avoiding the disadvantages of cell therapy. Furthermore, the ANS can replace the bladder regeneration model based on cell-binding scaffold materials and has the potential for clinical application. Statement of significanceThis study aimed to develop a gradient-degradable artificial acellular nanocomposite scaffold (ANS) loaded with stromal vascular fraction (SVF) secretome for rehabilitating bladders. Using various in vitro methods as well as rat- and zebrafish-based in vivo models, the developed ANS was assessed for efficacy and safety. Results indicated that the ANS achieved gradient degradation and slowly released the SVF secretome to promote tissue regeneration, even after long-term cryopreservation. Furthermore, ANS transplantation demonstrated a potent pro-angiogenic ability and induced M2 macrophage polarization to promote tissue regeneration and restore bladder function in a bladder replacement model. Our study demonstrates that ANS may replace bladder regeneration models based on cell-binding scaffold materials and have potential clinical application

Use of neuromodulation techniques in children with bladder and bowel dysfunction

One of the urgent problems in modern pediatric urology is a significant range of diseases associated with various dysfunctions of the bladder and rectum, which leads to the search for new effective methods that restore bladder function. From 20 to 40 % of cases of pelvic organ dysfunction in children are resistant to conservative treatment, which suggests that the use of a modern method of physiotherapy – electrical nerve stimulation – can be a treatment method when other methods do not have the desired effect.

Restoration of bladder function by inhibition of the Ninjurin-1 pathway in rat model of spinal cord injury

Restoration of bladder function by inhibition of the Ninjurin-1 pathway in rat model of spinal cord injury

Restoring bladder function using motor and sensory nerve transfers: a cadaveric feasibility study.

Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome. These transfers are applicable to only cases with low spinal segment injuries (sacral nerve root function is lost) and largely preserved lumbar function. Transfer of the posterior branch of the obturator nerve to the vesical branch of the pelvic nerve provides a feasible mechanism for patients to initiate detrusor contraction by thigh adduction. External urethra innervation (motor and sensory) may be accomplished by transfer of the vastus medialis nerve to the pudendal nerve. The sensory component of the pudendal nerve to the genitalia may be further enhanced by transfer of the saphenous nerve (sensory) to the pudendal nerve. The main limitations of coapting the nerve donors to their intrapelvic targets are the bifurcation or arborization points of the parent nerve. To ensure that the donor nerves had sufficient length and diameter, the authors sought to measure these parameters. Twenty-six pelvic and anterior thigh regions were dissected in 13 female cadavers. After the graft and donor sites were clearly exposed and the branches identified, the donor nerves were cut at suitable distal sites and then moved into the pelvis for tensionless anastomosis. Diameters were measured with calipers. The obturator nerve was bifurcated a mean ± SD (range) of 5.5 ± 1.7 (2.0-9.0) cm proximal to the entrance of the obturator foramen. In every cadaver, the authors were able to bring the posterior division of the obturator nerve to the vesical branch of the pelvic nerve (located internal to the ischial spine) in a tensionless manner with an excess obturator nerve length of 2.0 ± 1.2 (0.0-5.0) cm. The distance between the femoral nerve arborization and the anterior superior iliac spine was 9.3 ± 1.8 (6.5-15.0) cm, and the distance from the femoral arborization to the ischial spine was 12.9 ± 1.4 (10.0-16.0) cm. Diameters were similar between donor and recipient nerves. The chosen donor nerves were long enough and of sufficient caliber for the proposed nerve transfers and tensionless anastomosis.

A Scoping Review of Spinal Cord Stimulation for Improving Motor and Voiding Function Following Spinal Cord Injury

Spinal cord injury (SCI) can present with permanent loss of sensory and motor functions. Electrical stimulation of spinal neuronal circuits with epidural spinal cord stimulation (SCS) has the potential to enhance the excitability of motor neurons and restore bladder function to facilitate post-SCI recovery.

Postsurgical urodynamic study of total laparoscopic nerve-sparing radical hysterectomy for uterine cervical cancer.

To evaluate the impact on urodynamic results between the laparoscopic nerve-sparing radical hysterectomy (LRH) following a step-by-step procedure and abdominal nerve-sparing radical hysterectomy (ARH) for patients with uterine cervical cancer. This retrospective study enrolled 76 patients with cervical cancer: 35 in the LRH group and 41 in the ARH group. We analyzed their postoperative bladder function in a urodynamics study and examined the volume of resected pelvic nerves contained in parametrial sections using S-100 antibody staining. Estimated blood loss and hospital stay after operation for the LRH group were significantly better than those in the ARH group (p < 0.0001). As well, the number of harvested lymph nodes was significantly higher in the LRH group (p=0.044). There was no difference in perioperative complications between the two groups in this study. The 5-year disease-free survival rates and overall survival rates were 91.2% and 94.0% in the LRH group and 87.8% and 95.1% in the ARH group, both respectively. Although the median residual urine volume were no statistical differences between the LRH group and the ARH group, the recovery of postoperative bladder function (uroflowmetry) in the LRH group rapidly reached presurgery levels at 1month, and the LRH group had a smaller number of s-100 antibody stained nerves contained the parametrial sections. We demonstrated that LRH following a step-by-step procedure could achieve a higher level of prevention of damage to the bladder branch of the pelvic splanchnic nerve plexus and thus restore bladder function more rapidly.

Superior therapeutic activity of TGF-β-induced extracellular vesicles against interstitial cystitis.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disease characterized by incapacitating pelvic pain. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) are considered key mediators of the paracrine action of MSCs and show better biological activities than the parent MSCs, especially in the bladder tissue, which may be unfavorable for MSC survival. Here, we produced MSC-EVs using advanced three-dimensional (a3D) culture with exogenous transforming growth factor-β3 (TGF-β3) (T-a3D-EVs). Treatment with T-a3D-EVs led to significantly enhanced wound healing and anti-inflammatory capacities. Moreover, submucosal layer injection of T-a3D-EVs in chronic IC/BPS animal model resulted in restoration of bladder function, superior anti-inflammatory activity, and recovery of damaged urothelium compared to MSCs. Interestingly, we detected increased TGF-β1 level in T-a3D-EVs, which might be involved in the anti-inflammatory activity of these EVs. Taken together, we demonstrate the excellent immune-modulatory and regenerative abilities of T-a3D-EVs as observed by recovery from urothelial denudation and dysfunction, which could be a promising therapeutic strategy for IC/BPS.

Soft silicone‐based neural interface to modulate bladder function: chronic studies in awake behaving cats

Direct bladder wall stimulation has been attempted for decades to restore bladder function in people with spinal cord injury and other voiding dysfunctions. However, these efforts were limited by co‐activation of the urethra, legs and other pelvic organs at stimulus intensities that evoked bladder contractions. Neural interfaces for the detrusor muscle itself face several challenges due to its structure and the volume changes it undergoes in normal function. We designed a stretchable silicone net that can be placed around the bladder body to anchor a soft electrode array that interfaces directly with the base of bladder to generate bladder contractions.We created implantable versions of the electrode nets and tested them in chronic experiments. We implanted 5 healthy cats (4 females, 1 male) and tested them with and without anesthesia for 2‐3 months. A pressure catheter was implanted into the bladder to control volume and measure pressure.Bladder wall stimulation through various electrode configurations (monopolar, bipolar), temporal patterns (single electrode, sequential stimulation of multiple electrodes) and stimulus intensities were able to generate complete bladder emptying. In behaving cats, bladder wall stimulation at many different stimulus intensities elicited efficient voiding at physiological bladder pressures (med: 41, IQR: 27‐60 cmH2O). However, there was little relationship (r&lt;0.28) between stimulation amplitude and bladder pressure itself. Rather, stimulation amplitude had an effect on the time between stimulation onset and bladder contraction onset. At low stimulation amplitudes, there was a longer time between stimulation onset and voiding (med: 35s, IQR: 13.5‐68.2s) than occurred at higher amplitudes, which evoked more rapid voiding (med: 23s, IQR: 10‐45s). This contrasts with anesthetized tests, where stimulation at 3 ± 2 mA evoked increases in bladder pressure up to 35 cmH2O. These results suggest that stimulation of the bladder wall recruits sensory pathways leading to an urge to void, but that can be suppressed by the animals. For most of the duration of the implants, stimulation evoked functional voiding with consistent electrical stimulation thresholds. However, after several months there was a failure of an implanted bond that limited the overall duration of the implants.Chronic experiments demonstrate that these electrode nets can be used as a neural interface to generate or initiate comfortable, complete bladder emptying in awake behaving cats. Future efforts include understanding the effects of evoked sensations on voiding and improving the integrity of the bonding between the flexible conductors and the lead wire.

Adapting the Finetech-Brindley Sacral Anterior Root Stimulator for Bioelectronic Medicine.

The Finetech-Brindley Sacral Anterior Root Stimulator (SARS) is a low cost and reliable system. The architecture has been used for various bioelectric treatments, including several thousand implanted systems for restoring bladder function following spinal cord injury (SCI). Extending the operational frequency range would expand the capability of the system; enabling, for example, the exploration of eliminating the rhizotomy through an electrical nerve block. The distributed architecture of the SARS system enables stimulation parameters to be adjusted without modifying the implant design or manufacturing. To explore the design degrees-of-freedom, a circuit simulation was created and validated using a modified SARS system that supported stimulation frequencies up to 600 Hz. The simulation was also used to explore high frequency (up to 30kHz) behaviour, and to determine the constraints on charge delivered at the higher rates. A key constraint found was the DC blocking capacitors, designed originally for low frequency operation, not fully discharging within a shortened stimulation period. Within these current implant constraints, we demonstrate the potential capability for higher frequency operation that is consistent with presynaptic stimulation block, and also define targeted circuit improvements for future extension of stimulation capability.

Autophagy activation promotes the effect of iPSCs-derived NSCs on bladder function restoration after spinal cord injury

The role of autophagy in the transplantation of induced pluripotent stem cells (iPSCs)-derived neural stem cells (NSCs) to treat spinal cord injury (SCI) and neurogenic bladder was investigated in this study. NSCs derived from human iPSCs were identified by and immunofluorescence assay. To clarify the role of autophagy, iPSCs were treated with either an autophagy inducer (rapamycin), or an autophagy inhibitor (chloroquine). Cell Counting kit-8 (CCK-8), western blot and flow cytometry were used to detect the effect of autophagy on the viability and differentiation of iPSCs. Sixty Wistar rats were selected to establish the SCI model and treated with iPSCs-derived NSCs transplantation. The effect of autophagy on the bladder function of rats with different treatments was evaluated by Basso, Beattie, and Bresnahan (BBB) score, bladder function score, bladder weight measurement, Hematoxylin & Eosin (H&E) staining, and Masson staining. The results of in vitro experiment showed that rapamycin enhanced the cell activity of iPSCs, increased the number of nestin positive cells, up-regulated Beclin-1 and LC3BI/II expressions, and down-regulated p62 expression. And the results of in vivo experiment showed that rapamycin improved exercise ability and bladder function, partially restored bladder weight, and significantly reduced bladder tissue damage in SCI rats. However, chloroquine showed the opposite results. The differentiation of iPSCs into NSCs could be promoted by induced autophagy, while neurogenic bladder of SCI was restored by autophagy activation.

Restoring both continence and micturition after chronic spinal cord injury by pudendal neuromodulation

Neurogenic bladder management after spinal cord injury (SCI) is very challenging. Daily urethral catheterization is most commonly used to empty the bladder, which causes frequent infections of the lower urinary tract. This study reports a novel idea to restore both continence and micturition after SCI by an implantable pudendal nerve stimulator (PNS). The PNS was surgically implanted in four cats with complete SCI at T9-T10 spinal level and tested weekly for 13–14 weeks under awake conditions. These chronic SCI cats consistently exhibited large residual bladder volumes (average 40–50 ml) due to their inability to void efficiently, while urine leakage also occurred frequently. The PNS which consisted of stimulating the pudendal nerve at 20–30 Hz to trigger a spinal reflex bladder contraction and at the same time blocking the pudendal nerves bilaterally with 10 kHz stimulation to relax the external urethral sphincter and reduce the urethral outlet resistance successfully induced highly efficient (average 80–100%), low pressure (<50 cmH2O) voiding. The PNS at 5 Hz also promoted urine storage by inhibiting reflex bladder activity and increasing bladder capacity. At the end of 14-week chronic testing, low pressure efficient voiding induced by PNS was further confirmed under anesthesia by directly measuring voiding pressure using a bladder catheter inserted through the bladder dome. This study demonstrated the efficacy and safety of the PNS in awake chronic SCI cats, suggesting that a novel neuroprosthesis can be developed for humans to restore bladder function after SCI by stimulating and/or blocking the pudendal nerves.

Bladder pressure encoding by sacral dorsal root ganglion fibres: implications for decoding

Objective. We aim at characterising the encoding of bladder pressure (intravesical pressure) by a population of sensory fibres. This research is motivated by the possibility to restore bladder function in elderly patients or after spinal cord injury using implanted devices, so called bioelectronic medicines. For these devices, nerve-based estimation of intravesical pressure can enable a personalized and on-demand stimulation paradigm, which has promise of being more effective and efficient. In this context, a better understanding of the encoding strategies employed by the body might in the future be exploited by informed decoding algorithms that enable a precise and robust bladder-pressure estimation. Approach. To this end, we apply information theory to microelectrode-array recordings from the cat sacral dorsal root ganglion while filling the bladder, conduct surrogate data studies to augment the data we have, and finally decode pressure in a simple informed approach. Main results. We find an encoding scheme by different main bladder neuron types that we divide into three response types (slow tonic, phasic, and derivative fibres). We show that an encoding by different bladder neuron types, each represented by multiple cells, offers reliability through within-type redundancy and high information rates through semi-independence of different types. Our subsequent decoding study shows a more robust decoding from mean responses of homogeneous cell pools. Significance. We have here, for the first time, established a link between an information theoretic analysis of the encoding of intravesical pressure by a population of sensory neurons to an informed decoding paradigm. We show that even a simple adapted decoder can exploit the redundancy in the population to be more robust against cell loss. This work thus paves the way towards principled encoding studies in the periphery and towards a new generation of informed peripheral nerve decoders for bioelectronic medicines.

Needs, priorities, and attitudes of individuals with spinal cord injury toward nerve stimulation devices for bladder and bowel function: a survey.

Study Design:Survey.Objectives:To investigate the needs and priorities of people with spinal cord injury for managing neurogenic bladder and bowel function and to determine their willingness to adopt neuromodulation interventions for these functions.Methods:Anonymous online survey. It was advertised by word-of-mouth by community influencers and social media, and by advertisement in newsletters of advocacy groups.Results:Responses from 370 individuals (27% female, 73% male) were included. Bladder emptying without catheters was the top priority for restoring bladder function, and maintaining fecal continence was the top priority for restoring bowel function. The biggest concerns regarding external stimulation systems were wearing a device with wires connecting to electrodes on the skin and having to don and doff the system daily as needed. The biggest concerns for implanted systems were the chances of experiencing problems with the implant that required a revision surgery or surgical removal of the whole system. Respondents were willing to accept an external (61%) or implanted (41%) device to achieve improved bladder or bowel function.Conclusions:Bladder and bowel dysfunction remain important unmet challenges for individuals living with SCI who answered our survey. These individuals are willing to accept some potential risks of nerve stimulation approaches given potential benefits. Additional consumer input is critical for guiding both research and translation to clinical use and personalized medicine.

Spinal cord stimulation for the restoration of bladder function after spinal cord injury.

Spinal cord injury (SCI) results in the inability to empty the bladder voluntarily, and neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD) negatively impact both the health and quality of life of persons with SCI. Current approaches to treat bladder dysfunction in persons with SCI, including self-catheterisation and anticholinergic medications, are inadequate, and novel approaches are required to restore continence with increased bladder capacity, as well as to provide predictable and efficient on-demand voiding. Improvements in bladder function following SCI have been documented using a number of different modalities of spinal cord stimulation (SCS) in both persons with SCI and animal models, including SCS alone or SCS with concomitant activity-based training. Improvements include increased volitional voiding, voided volumes, bladder capacity, and quality of life, as well as decreases in NDO and DSD. Further, SCS is a well-developed therapy for chronic pain, and existing Food And Drug Administration (FDA)-approved devices provide a clear pathway to sustainable commercial availability and impact. However, the effective stimulation parameters and the appropriate timing and location of stimulation for SCS-mediated restoration of bladder function require further study, and studies are needed to determine underlying mechanisms of action.

SPARC: Soft silicone electrode net for modulating bladder function

Bladder wall stimulation has been attempted for many decades to restore bladder function in people with spinal cord injury and other voiding dysfunctions. However, these efforts were limited by current spread to urethral structures, activation of the legs and co‐recruitment of other pelvic organs. Neural interfaces for the detrusor muscle itself face several challenges due to its unique structure and function. To directly modulate the bladder and urethra, we designed a stretchable electrode array that interfaces directly with the surface of these organs. With a stretchable electrode array that conforms to the bladder wall, we aim to create direct organ interface electrodes to stimulate and record from the bladder wall.Acute experiments in isoflurane‐anesthetized cats (n=9, 8 males, 1 female) were performed to characterize the functional and electromechanical properties of this polymer electrode. Nerve cuffs were placed bilaterally on the hypogastric and pelvic nerves to record neural activity during bladder wall stimulation. Fine wire electromyography (EMG) electrodes were placed in gluteal muscle as well as the external anal and urethral sphincters to measure current spread. A pressure catheter was placed transurethrally to record pressure and infuse saline into the bladder. Elastic electrodes were placed on the dorsal, ventral, and both lateral aspects of the bladder. In an isovolumetric bladder state, each electrode was stimulated (at amplitude: 2–8 mA, frequency: 3 – 33 Hz, pulse width: 1ms) while recording bladder pressure and compound action potentials in the instrumented nerves. To determine the mechanism of action, pelvic and hypogastric nerves were transected sequentially while measuring bladder pressure.We found that electrodes positioned near the bladder neck around the ureterovesical junction elicited the largest bladder contractions up to ~45 cmH2O while other locations such as the bladder dome generated significantly smaller contractions (~10 cmH2O). Bipolar stimulation on the bladder limited activation of the urethral sphincter and hind limbs through current spread compared to monopolar stimulation as shown by significant reduction in EMG activity with similar increases in bladder pressure. EMG recorded from the bladder wall had a directly proportional relation between frequency and volume thereby depicting detrusor muscle activity. Finally, we found that the passive mechanical effects of the silicone net around the bladder had a minimal impact (&lt; 5 cmH2O) on bladder pressure. Following nerve transection, single electrode stimulation on the ureterovesical junction resulted in smaller pressure increases compared to before transection, whereas there was no change in the pressures evoked by multi‐electrode stimulation.These soft silicone electrode nets can be used as a neural interface to generate bladder contractions in conditions where the bladder is underactive or atonic and enables continuous monitoring of detrusor EMG to monitor bladder state. Bladder wall stimulation acts through both direct‐efferent and reflex‐driven afferent mechanisms depending on stimulation location and charge.Support or Funding InformationNIH SPARC OT2OD025297

MP54-01 SOFT SILICONE ELECTRODE NET FOR MODULATING BLADDER FUNCTION

INTRODUCTION AND OBJECTIVE: Bladder wall stimulation has been attempted for many decades to restore bladder function in people with spinal cord injury and other voiding dysfunctions. However, these efforts were limited by current spread to urethral structures, activation of the legs and co-recruitment of other pelvic organs. Neural interfaces for the detrusor muscle itself face several challenges due to its unique structure and function. To directly modulate the bladder and urethra, we designed a stretchable electrode array that interfaces directly with the surface of these organs. With a stretchable electrode array that conforms to the bladder wall, we aim to create direct organ interface electrodes to stimulate and record from the bladder wall. METHODS: Acute experiments in isoflurane-anesthetized cats (n=9, 8 males, 1 female) were performed to characterize the functional and electromechanical properties of this polymer electrode. Nerve cuffs were placed bilaterally on the hypogastric and pelvic nerves to record neural activity during bladder wall stimulation. Fine wire electromyography (EMG) electrodes were placed in gluteal muscle as well as the external anal and urethral sphincters to measure current spread. A pressure catheter was placed transurethrally to record pressure and infuse saline into the bladder. Elastic electrodes were placed on the dorsal, ventral, and both lateral aspects of the bladder. In an isovolumetric bladder state, each electrode was stimulated (at amplitude: 2-8 mA, frequency: 3 -33 Hz, pulse width: 1ms) while recording bladder pressure and compound action potentials in the instrumented nerves. RESULTS: We found that electrodes positioned near the bladder neck around the ureterovesical junction elicited the largest bladder contractions up to ∼45 cmH2O while other locations such as the bladder dome generated significantly smaller contractions (∼10 cmH2O). Bipolar stimulation on the bladder limited activation of the urethral sphincter and hind limbs through current spread compared to monopolar stimulation as shown by significant reduction in EMG activity with similar increases in bladder pressure. EMG recorded from the bladder wall had a directly proportional relation between frequency and volume thereby depicting detrusor muscle activity. Finally, we found that the passive mechanical effects of the silicone net around the bladder had a minimal impact (< 5 cmH2O) on bladder pressure. CONCLUSIONS: These soft silicone electrode nets can be used as a neural interface to generate bladder contractions in conditions where the bladder is underactive or atonic and enables continuous monitoring of detrusor EMG to monitor bladder state. Source of Funding: This project is supported through NIH SPARC OT2OD025297

Chlorogenic acid attenuates cyclophosphamide-induced rat interstitial cystitis

AimsThis study aimed to investigate the therapeutic effect and molecular mechanism of chlorogenic acid (CGA) on cyclophosphamide (CYP)-induced rat interstitial cystitis (IC). Materials and methodsAn animal model of IC was established by intraperitoneal injection of CYP in female Sprague-Dawley rats. Eighty rats were randomly assigned to four groups: negative control (NC), NC treated with CGA (NC + CGA), IC, and IC treated with CGA (IC + CGA). Bladder urination function was assessed by analyzing urodynamic parameters. The expression of apoptosis-related proteins and inflammatory biomarkers in bladder specimens was detected using western blot and immunohistochemistry analysis. Key findingsCompared with the IC group, bladder urinary function was significantly improved in the IC + CGA group. CGA treatment reduced inflammatory damage in the bladder tissue of IC rats. Caspase3 and Bax expression was higher while Bcl-2 expression was lower in the IC group compared to the IC + CGA group. In addition, there were significant differences between the groups in the expression levels of inflammatory biomarkers in the bladder tissue. Furthermore, CGA could inhibit CYP-induced MAPK/NF-κB phosphorylation in the rat bladder tissue. SignificanceIn a CYP-induced rat model of IC, CGA could reduce inflammation and apoptosis, thus partially restoring bladder function, and the MAPK/NF-κB pathway was probably involved in it.

Anatomical feasibility of anastomosing intercostal nerves (D10&D11) and subcostal nerve (D12) to S2 ventral root and lumbar plexus for management of bladder function after spinal cord injury

ObjectiveThe transfer of peripheral nerves originating above the level of injured spinal cord into the nerves/roots below the injury is a promising approach. It facilitates the functional recovery in lower extremity, bladder/bowel and sexual function in paraplegics. We assessed anatomical feasibility of transfer of lower intercostal nerves to S2 ventral root in human cadaver for management of neurogenic bladder dysfunction in patients with spinal cord injury. MethodsStudy was performed in five formalin fixed cadavers. Cadavers were placed in prone position. A transverse incision was made along 11th ribs on both sides and 10th, 11th Intercostal nerves (ICN) and subcostal nerve were harvested up to maximum possible length. In four cadavers the ventral root of S2 was exposed by endoscope and in one by the standard open laminectomy. Intercostal nerves were brought down to lumbo-sacral region, S2 ventral root was cut cranially and feasibility of intercostal to S2 anastomosis was assessed. ResultsThe mean length of intercostal nerves was 18.4 cm for the 10th 19.5 cm for the 11th and 22.15 cm for the subcostal nerve. The length of harvested nerve and the nerve length necessary to perform sacral roots neurotization were possible in all cases by only by subcostal nerve while T11 and T10 ICN fall short of the required length. ConclusionFor Spinal cord lesions located at the conus, subcostal nerve could be connected to ventral root of S2 in an attempt to restore bladder function while 10th and 11th ICN had enough length to neurotize lumbar plexus.