Sacral Cord Research Articles

A New Rat Model of Sacral Cord Injury Producing a Neurogenic Bladder and Its Functional and Mechanistic Studies.

Sacral spinal cord injury (SSCI) can disrupt bladder neuromodulation and impair detrusor function. Current studies provide limited information on the histologic and genetic changes associated with SSCI-related neurogenic lower urinary tract dysfunction (NLUTD), resulting in few treatment options. This study aimed to establish a simple animal model of SSCI to better understand the disease progression. Ninety 8-week-old Sprague-Dawley (SD) rats were randomly separated into sham operation and SSCI groups. The SSCI group underwent sacral spinal cord injury, while the sham group did not. Urodynamic and histological assessments were conducted at various intervals (1, 2, 3, 4, and 6 weeks) post-injury to elucidate the disease process. Urodynamic examinations revealed significant bladder dysfunction in the SSCI group compared to the sham group, stabilizing around 3-4 weeks post-injury. Histological examination, including hematoxylin-eosin and Masson's trichrome staining, correlated these functional changes with bladder microstructural alterations. RNA-seq was performed on bladder tissues from the sham group and SSCI group at 6 weeks to identify differentially expressed genes and pathways. Selected genes were further analyzed using polymerase chain reaction (PCR). The findings indicated a pronounced inflammatory response in the first 2 weeks post-SSCI, progressing to bladder fibrosis at 3-4 weeks. In conclusion, this study presents a reliable, reproducible, and straightforward SSCI model, providing insights into bladder functional and morphological alterations post-SSCI and laying the groundwork for future therapeutic research.

Functional Outcome in Patients With Anorectal Malformation With Recto-prostatic or Recto-bulbar Urethral Fistula and Comparison Between Different Surgical Approaches: A Multi-center Study

PurposeTo analyze and compare the outcomes in patients with anorectal malformation with rectoprostatic and rectourethral fistula between laparoscopic-assisted anorectoplasty (LAARP) versus posterior sagittal anorectoplasty (PSARP). MethodWe performed a retrospective review on all males with anorectal malformation (ARM) with recto-prostatic (ARM-RP) or recto-bulbar urethral fistula (ARM-RB) treated in five tertiary paediatric surgical centres in the past 25 years. Defecative function was assessed using the Krickenbeck classification and Kelly's score. Functional outcomes between patients with LAARP and PSARP were compared. ResultsThere were a total of 136 males with ARM-RP and ARM-RB for analysis, among which 73 (53.7%) had ARM-RP and 63 (46.3%) had ARM-RB. The median age of the patients was 9.4 years (range 0.8–24.7 years) and the median age at operation was 0.4 years (0 day–3.1 years). 57 (41.9%) and 79 patients (58.1%) underwent PSARP and LAARP respectively. 34 patients (25%) had VACTERL association. 111 (81.6%) and 103 patients (75.7%) had sacral and spinal cord anomalies respectively. 19 patients (13.9%) eventually required Malone's Antegrade Continence Enema (MACE).For the comparison between PSARP and LAARP, no difference in Kelly scores (4.58 ± 1.63 versus 4.67 ± 1.36) was identified (p = 0.79). Logistic regression for voluntary bowel movement showed that VACTER association (p = 0.02) and fistula location (p = 0.01) were significant prognostic factors, whereas the operation approach (PSARP or LAARP) was not (p = 0.65). ConclusionVACTERL association and fistula location were significant prognostic factors for voluntary bowel movement, and there appeared to be no significant difference in functional outcome between PSARP and LAARP. Level of EvidenceIV.

Perioperative Histologically Controlled Fistula Resection in Patients with Imperforate Anus and Perineal Fistula.

Postoperative constipation (PC) in patients with imperforate anus and perineal fistula (PF) has been reported in up to 60%. Histological studies of PF revealed innervation anomalies which seem to be one of the reasons for PC. Perioperative histologically controlled fistula resection (PHCFR) allows appropriate resection of PF and pull-down normoganglionic rectum at the time of posterior sagittal anorectoplasty (PSARP). A total of 665 patients with anorectal malformations underwent surgery between 1991 and 2021. Of these, 364 presented PF; 92 out of them (41 F) were studied. Patients with sacral and spinal cord anomalies, neurological disorders, and cut-back anoplasty were excluded. PSARP was done on all patients. Hematoxylin-eosin staining and NADH Tetrazolium-reductase histochemical method were used. Four and more ganglion cells in the myenteric plexus represented a sufficient length of the resection. The continence was scored according to the modified Krickenbeck scoring system. Final scores ranged from 1 to 7 points. Values are given as median. A total of 65 (70.7%) patients presented an aganglionic segment in PF, and 27 patients presented hypoganglionosis. The median length of the resected fistula was 25 mm (interquartile range [IQR]: 20-30). The median total continence score was 7 (IQR: 6-7). Post-op constipation was observed in 6/92 (6.5%) patients. PHCFR diminished PC to 6.5% of patients.

Effect of Yiyuan moxibustion on urodynamics and TRPV4/ATP/P2X5 signal pathway of bladder tissue in rats with neurogenic bladder after sacral cord injury.

To observe the effect of Yiyuan moxibustion on urodynamics and the expressions of transient receptor potential vanilloid 4 (TRPV4), adenosine triphosphate (ATP), tyrosine protein kinase KIT (C-Kit) and adenosine triphosphate receptor P2X5 in bladder tissue of rats with detrusor reflex-free neurogenic bladder (NB) after sacral cord injury (SCI), so as to explore its mechanism in promoting the recovery of urination function of NB rats. Female SD rats were randomly divided into sham operation, model, Yiyuan moxibustion, Yiyuan moxibustion+inhibitor (combination) and inhibitor groups, with 12 rats in each group. The model of detruser reflex-free NB after sacral SCI was established by modified Hassan Shaker spinal cord transection method. The behavioral score of Basso Beasttie Bresnahan (BBB) and urodynamic indexes were used to evaluate the model of rats after operation. Fifteen days after modeling, Yiyuan moxibustion was applied to "Shenque" (CV8) and "Guanyuan" (CV4) for 20 min, once daily for 14 days. Rats of the inhibitor and combination groups were given intravesical instillation of HC067047 (1 mL, 1 μmol/L, 30 min). After the interventions, urodynamics was used to evaluate the bladder function of rats. HE staining was used to observe the morphology of bladder tissue. ATP content in bladder tissue was detected by colorimetric method. The positive expression rates of C-Kit and their receptor P2X5 in bladder tissue were observed by immunofluorescence double labeling method, and TRPV4, C-Kit, and P2X5 protein expression levels in bladder tissue were detected by Western blot. Compared with the sham operation group, the maximum bladder capacity and bladder compliance of rats in the model group were increased (P<0.01), the leak point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and the protein expression levels of TRPV4, C-Kit, P2X5 in bladder tissue were decreased (P<0.01). In comparison with the model and combination groups, the Yiyuan moxibustion group showed a decrease in maximum bladder capacity and bladder compliance (P<0.01), an increase in leakage point pressure, ATP content, the possitive expression rates of C-Kit and P2X5, and TRPV4, C-Kit, and P2X5 protein expression levels (P<0.01, P<0.05)；However, these indicators showed opposite trends in the inhibitor group (P<0.01, P<0.05). Yiyuan moxibustion can improve the urodynamics and bladder function in rats with bladder detrusor nonreflective after SCI, which may be related to its effect in activating the TRPV4 channel in bladder tissue, promoting the release of ATP from bladder epithelium, thus increasing the expression of bladder Cajal interstitial cells and their purinergic P2X5 receptors.

New insight on the enteric cholinergic innervation of the pig colon by central and peripheral nervous systems: reduction by repeated loperamide administration.

The central and peripheral nervous systems provide cholinergic innervation in the colon. The ability to assess their neuroanatomical distinctions is still a challenge. The pig is regarded as a relevant translational model due to the close similarity of its enteric nervous system (ENS) with that of human. Opioid-induced constipation is one of the most common side effects of opioid therapy. We developed an approach to differentiate the central and peripheral cholinergic innervation of the pig colon using double immunolabeling with a novel mouse anti-human peripheral type of choline acetyltransferase (hpChAT) antibody combined with a rabbit anti-common type of ChAT (cChAT) antibody, a reliable marker of cholinergic neurons in the central nervous system. We examined their spatial configurations in 3D images of the ENS generated from CLARITY-cleared colonic segments. The density was quantitated computationally using Imaris 9.7. We assessed changes in the distal colon induced by daily oral treatment for 4 weeks with the μ opioid receptor agonist, loperamide (0.4 or 3 mg/kg). The double labeling showed strong cChAT immunoreactive (ir) fibers in the cervical vagus nerve and neuronal somata and fibers in the ventral horn of the sacral (S2) cord while hpChAT immunoreactivity was visualized only in the ENS but not in the vagus or sacral neural structures indicating the selectivity of these two antibodies. In the colonic myenteric plexus, dense hpChAT-ir neurons and fibers and varicose cChAT-ir fibers surrounding hpChAT-ir neurons were simultaneously visualized in 3D. The density of cChAT-ir varicose fibers in the outer submucosal plexus of both males and females were higher in the transverse and distal colon than in the proximal colon and in the myenteric plexus compared to the outer submucosal plexus and there was no cChAT innervation in the inner submucosal plexus. The density of hpChAT in the ENS showed no segmental or plexus differences in both sexes. Loperamide at the highest dose significantly decreased the density hpChAT-ir fibers + somata in the myenteric plexus of the distal colon. These data showed the distinct density of central cholinergic innervation between myenteric and submucosal plexuses among colonic segments and the localization of cChAT-ir fibers around peripheral hpChAT neurons in 3D. The reduction of cholinergic myenteric innervation by chronic opiate treatment points to target altered prokinetic cholinergic pathway to counteract opiate constipation.

Neuromodulation for functional upper gastrointestinal diseases.

Neuromodulation has recently received a great deal of attention among academic institutions, government funding agents and industries. This mini-review focuses on methods and applications as well as mechanisms of various neuromodulation methods in treating functional diseases of the upper gastrointestinal tract. First, the methods of various neuromodulation are introduced, including direct electrical stimulation at various peripheral nerves, such as the vagus nerve, sacral nerve and spinal cord, direct gastrointestinal electrical stimulation and noninvasive/transcutaneous electrical stimulation. Then, literature search was performed on the clinical applications of these neuromodulation methods for treating gastroesophageal reflux disease, functional dyspepsia and gastroparesis. Due to nature of the mini-review, the search results are selectively presented based on the expert opinions. Finally, a perspective is provided based on the author's own experience in this field of research.

The implications of neurogenic bowel dysfuncton for urinary tract reconstruction in neurogenic urinary tract dysfunction: An International Continence Society working group report

Introduction:The consequences of neurogenic bowel dysfunction in patients with neurogenic lower urinary tract disease requiring urinary tract reconstruction with bowel harvest remains unclear. A working group was formed by the International Continence Society (ICS) to generate a consensus statement highlighting the key issues to be addressed and optimised peri-operatively. Methods:Nominal group technique was used to derive consensus. Principal aspects of assessment and surgery decision-making were agreed and a series of statements was generated by a core focus group of experts, which were subsequently modified and ratified by the wider working group. This was followed by final voting by the full working group. Results:General considerations included the importance of understanding the neurological condition in terms of degree of disability, prognosis and risk of progression, an assessment of cognition and dexterity and an inter-disciplinary assessment to ensure suitability and feasibility of surgery. Peri-operative recommendations included using an enhanced recovery after surgery (ERAS) protocol when appropriate and taking additional precautions if there is a risk of autonomic dysreflexia or the presence of implants such as ventriculo-peritoneal shunts, baclofen pumps, sacral or spinal cord stimulators. Extra consideration must be taken post-operatively to minimise the risk of venous thrombo-embolism formation, formation/exacerbation of pressure sores and long-term bowel disturbance. Conclusion:The consensus opinion indicates that urinary tract reconstruction using bowel segments is feasible in carefully selected and optimised patients with neurogenic bowel dysfunction, provided the potential implications for serious adverse events are carefully considered and there is access to appropriate inter-disciplinary expertise.

Urological Management of the Spinal Cord-Injured Patient: Suggestions for Improving Intermittent Catheterization and Reflex Voiding

Spinal cord injury can either be complete with no neural communication across the injury level or incomplete with limited communication. Similarly, motor neuron injuries above the sacral spinal cord are classified as upper motor neuron injuries, while those inside the sacral cord are classified as lower motor neuron injuries. Specifically, we provide recommendations regarding the urological management of complete upper motor neuron spinal cord injuries; however, we also make limited comments related to other injuries. The individual with a complete upper motor neuron injury may encounter five lower urinary tract conditions: first, neurogenic detrusor overactivity causing urinary incontinence; second, neurogenic detrusor underactivity resulting in high post-void residual volumes; third, detrusor sphincter dyssynergia, which is contraction of striated and/or smooth muscle urethral sphincters during detrusor contractions; fourth, urinary tract infection; and fifth, autonomic dysreflexia during detrusor contractions, which produces high blood pressure as well as smooth muscle detrusor sphincter dyssynergia. Intermittent catheterization is the recommended urinary management method because it addresses the five lower urinary tract conditions and has good long-term outcomes. This method uses periodic catheterizations to drain the bladder, but also needs bladder inhibitory interventions to prevent urinary incontinence between catheterizations. Primary limitations associated with this management method include difficulties with the multiple catheterizations, side effects of bladder inhibitory medications, and urinary tract infections. Three suggestions to address these concerns include the use of low-friction catheters, wireless, genital-nerve neuromodulation for bladder inhibition, and consideration of urine egress into the urethra as a risk factor for UTI as well as egress treatment. The second management method is reflex voiding. This program uses external condoms for urine collection in males and diapers for females. Suprapubic tapping is used to promote bladder contractions. This method is not recommended because it has high rates of medical complications. In particular, it is associated with high detrusor pressure, which can lead to ureteral reflux and kidney pathology. Botulinum toxin injection into the urethral striated sphincter can manage detrusor sphincter dyssynergia, reduce voiding pressures, and risks to the kidney. We suggest a modified method for botulinum toxin injections as well as five additional methods to improve reflex voiding outcomes. Finally, the use of intermittent catheterization and reflex voiding for individuals with incomplete spinal injuries, lower motor neuron injuries and multiple scleroses are briefly discussed.

Effects of Sacral Nerve Stimulation on Neuronal Nitric Oxide Synthase in the Colon and Sacral Cord of Rats With Defecation Disorder After Spinal Cord Injury

This study aimed to determine the effects of sacral nerve electrical stimulation (SNS) on neuronal nitric oxide synthase (nNOS) in the colon and sacral cord of rats with defecation disorder after spinal cord injury (SCI). Rats with severe SCI (T10) were used as models and randomly divided into an SCI group and an SNS group. After 14 days of treatment, the intestinal transport function was assessed. Finally, the differences in nNOS immunoreactive cells, protein levels, nNOS mRNA, and NO content in the colon and sacral cord tissues were estimated using immunohistochemistry, Western blot, real-time polymerase chain reaction, and nitrate reductase method. The intestinal transport function of the SNS group was superior to that of the SCI group (P < 0.05). The average optical density of nNOS immunoreactive positive cells in the SCI group were significantly increased compared with those in the sham group. The content of NO of the SCI group significant increased compared with those of the sham group and the SNS group (both P < 0.01). The nNOS mRNA and protein expression was higher in the SCI group than in the sham group (P < 0.01), while that in the SNS group was significantly lower than that in the SCI group. SNS could reduce nNOS expression in the colon and sacral cord of SCI rats. This reduction may be an important neuromodulation mechanism for SNS to improve defecation reflex and promote the recovery of intestinal transit function.

MP08-15 HIGH-RESOLUTION EPIDURAL SPINAL CORD STIMULATION (HR-SCS) EVOKES SELECTIVE MICTURITION AND CONTINENCE REFLEXES THROUGH A FREQUENCY-DEPENDENT EFFECT GOVERNED BY DISTINCT NEURAL CIRCUITS

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology (MP08)1 Sep 2021MP08-15 HIGH-RESOLUTION EPIDURAL SPINAL CORD STIMULATION (HR-SCS) EVOKES SELECTIVE MICTURITION AND CONTINENCE REFLEXES THROUGH A FREQUENCY-DEPENDENT EFFECT GOVERNED BY DISTINCT NEURAL CIRCUITS Chaitanya Gopinath, Maria K. Jantz, Ritesh Kumar, Bryan L. McLaughlin, and Robert A. Gaunt Chaitanya GopinathChaitanya Gopinath More articles by this author , Maria K. JantzMaria K. Jantz More articles by this author , Ritesh KumarRitesh Kumar More articles by this author , Bryan L. McLaughlinBryan L. McLaughlin More articles by this author , and Robert A. GauntRobert A. Gaunt More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001981.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Spinal cord stimulation (SCS) has been explored for controlling lower urinary tract function in experimental and clinical settings. However, there are no mechanistic and reproducible approaches to evoke both micturition and continence reflexes. Here, we demonstrate that epidural SCS can selectively evoke micturition and continence behaviors in both isovolumetric and cystometric studies in feline anesthetized animal model. Our results indicate the existence of two distinct frequency-dependent neural circuits mediating continence and micturition evoked by varying stimulus frequencies. METHODS: Three male and three female cats (n=6) were anesthetized with α-chloralose after initial surgical preparations under isoflurane anesthesia. Nerve cuffs were placed unilaterally on the pelvic nerve, pudendal nerve and its branches (sensory, deep perineal and caudal rectal nerves). HR-SCS electrodes (Ripple Neuro, Micro-Leads Medical) were placed on the epidural surface of sacral cord and cauda equina. Stimulation pulse trains with amplitudes between 200-800 µA were delivered through SCS electrodes while recording bladder pressure and compound action potentials in the peripheral nerve cuffs. Electromyograms from the pelvic floor and urethral sphincter, as well as bladder pressure data were collected, first under isovolumetric bladder conditions and later during filling cystometries. RESULTS: Epidural SCS through many electrodes was able to elicit functional changes in the bladder and urethra. We also identified bipolar electrode pairs that evoked a frequency-dependent effect. Stimulation at 3 Hz stimulation evoked a continence reflex, while the same electrodes evoked a voiding reflex when the stimulation frequency was changed to 33 Hz. Inhibition through 3 Hz stimulation was particularly robust and resulted in abolishing all non-voiding contractions (NVCs) and decreasing the bladder pressure to its baseline value. Voiding under 33 Hz was incomplete and varied between 20-50% of the infused volume. In 3 animals, an acute spinalization at T10 abolished all 33 Hz-evoked responses suggesting that this neural circuit requires an intact spino-bulbo-spinal reflex. The 3 Hz continence reflex remained unaffected by spinalization suggesting a local reflex in the lumbosacral spinal cord. CONCLUSIONS: HR-SCS can selectively evoke continence and micturition reflexes through a unique frequency-dependent effect. Source of Funding: NIH OT2OD024908 and Craig H. Neilsen Foundation—476681 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e155-e156 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Chaitanya Gopinath More articles by this author Maria K. Jantz More articles by this author Ritesh Kumar More articles by this author Bryan L. McLaughlin More articles by this author Robert A. Gaunt More articles by this author Expand All Advertisement Loading ...

Single axonal morphology reveals high heterogeneity in spinocerebellar axons originating from the lumbar spinal cord in the mouse.

Among the spinocerebellar projections vital for sensorimotor coordination of limbs and the trunk, the morphology of spinocerebellar axons originating from the lumbar cord has not been well characterized compared to those from thoracic and sacral cords. We reconstructed 26 single spinocerebellar axons labeled by biotinylated dextran injections into the gray matter of the lumbar spinal cord in mice. Axon terminals were mapped with the zebrin pattern of the cerebellar cortex. Reconstructed axons were primarily classified into ipsilaterally and contralaterally ascending axons, arising mainly from the dorsal and ventral horns, respectively. The majority of ipsilateral and contralateral axons took the dorsal-medullary and ventral-pontine pathways, respectively. The axons of both groups terminated mainly in the vermal and medial paravermal areas of lobules II-V and VIII-IXa, often bilaterally but predominantly ipsilateral to the axonal origin, with a weak preference to particular portions of zebrin stripes. The ipsilateral axons originating from the medial dorsal horn in the upper lumbar cord (n=3) had abundant (43-147) mossy fiber terminals and no medullary collaterals. The ipsilateral axons originating from the lateral dorsal horn in the lower lumbar cord (n=9) and the contralateral axons (n=14) showed remarkable morphology variations. The number of their mossy fiber terminals varied from 2 to 172. Their collaterals, observed in 17 axons out of 23, terminated mainly in the medial cerebellar nucleus, nucleus X, and lateral reticular nucleus in various degrees. The results indicated that the lumbar spinocerebellar projection contains highly heterogeneous axonal populations regarding their pathway, branching, and termination patterns.

Disease surveillance in England and Wales, April 2021

Disease surveillance in England and Wales, April 2021

Rhythmogenic networks are potently modulated by activation of muscarinic acetylcholine receptors in the rodent spinal cord.

Electrical stimulation of the spinal cord is a potent means for activating mammalian stepping in the absence of the descending control from the brain. Previously, we have shown that stimulation of pain delivering (Aδ) sacrocaudal afferents (SCA) has a powerful capacity to activate the sacral and lumbar rhythmogenic networks in the neonatal rodent spinal cord. Relatively little is known about the neural pathways involved in activation of the locomotor networks by Aδ afferents, on their mechanism of action and on the possibility to modulate their activity. We have shown that elevation of the endogenous level of acetylcholine at the sacral cord by blocking cholinesterase could modulate the SCA-induced locomotor rhythm in a muscarinic receptor-dependent mechanism. Here, we review these and more recent findings and report that controlled stimulation of SCA in the presence of muscarine is a potent activator of the locomotor network. The possible mechanisms involved in the muscarinic modulation of the locomotor rhythm are discussed in terms of the differential projections of sacral relay neurons, activated by SCA stimulation, to the lumbar locomotor rhythm generators, and to their target motoneurons. Altogether, our studies show that manipulations of cholinergic networks offer a simple and powerful means to control the activity of locomotor networks in the absence of supraspinal control. Cover Image for this issue: https://doi.org/10.1111/jnc.15079.

Intraspinal stimulation with a silicon-based 3D chronic microelectrode array for bladder voiding in cats

Objective. Bladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury (SCI). Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental SCI. Here, we continue the development of the intraspinal microstimulation array technology to evaluate its ability to provide more focused and reliable bladder control in the feline animal model. Approach. For the first time, a mechanically robust intraspinal multisite silicon array was built using novel microfabrication processes to provide custom-designed tip geometry and 3D electrode distribution. Long-term implantation was performed in eight spinally intact animals for a period up to 6 months, targeting the dorsal gray commissure area in the S2 sacral cord that is known to be involved in the coordination between the bladder detrusor and the external urethral sphincter. Main results. About one third of the electrode sites in the that area produced micturition-related responses. The effectiveness of stimulation was further evaluated in one of eight animals after spinal cord transection (SCT). We observed increased bladder responsiveness to stimulation starting at 1 month post-transection, possibly due to supraspinal disinhibition of the spinal circuitry and/or hypertrophy and hyperexcitability of the spinal bladder afferents. Significance. 3D intraspinal microstimulation arrays can be chronically implanted and provide a beneficial effect on the bladder voiding in the intact spinal cord and after SCT. However, further studies are required to assess longer-term reliability and safety of the developed intraspinal microstimulation array prior to eventual human translation.

Effects of sacral nerve electrical stimulation on 5‑HT and 5‑HT3AR/5‑HT4R levels in the colon and sacral cord of acute spinal cord injury rat models.

Spinal cord injury (SCI) often leads to defecation dysfunction. Sacral nerve electrical stimulation (SNS) therapy could improve defecation function. The present study aimed to assess SNS therapy, with regard to the levels of serotonin (5-HT) and its receptors (5-HT3AR and 5-HT4R) in the colon and sacral cord, a rat model of acute severe SCI was used. This rat model was made using the New York University Impactor device. Model rats were randomized to the SCI and SNS (electrical stimulation on the S3 nerve) groups. After 14 days of treatment, enteric transmission function was assessed. 5-HT and 5-HT3AR/5-HT4R were measured by ELISA, quantitative PCR, immunohistochemistry and western blotting. In SCI rats, SNS significantly increased the quantity of feces, shortened the time to the first fecal passage, and improved fecal texture and colon histology. SNS elevated 5-HT contents in the colon and spinal cord, and enhanced 5-HT3AR/5-HT4R protein expression and distribution in the colonic myenteric plexus and mucosa, sacral intermediolateral nucleus and dorsal horn. SNS upregulated the relative expression levels of 5-HT3AR/5-HT4R mRNA and protein in the colon and spinal cord. SNS can improve defecation and accelerate the recovery of colonic transmission functions in rat models of acute SCI. These effects involved upregulation of the 5-HT/5-HT3AR/5-HT4R axes.

The correlation between diffusion tensor imaging of the sacral cord and bladder contractility in people with tetraplegia.

Cross-sectional descriptive study. To compare the diffusion tensor imaging (DTI) changes of the sacral cord in people with complete cervical spinal cord injury (SCI) and neurogenic bladder versus people without SCI, and to explore the relationship between sacral cord DTI changes and bladder contractility. First Affiliated Hospital of Soochow University, Jiangsu Province, China. Forty participants were included: 25 participants with complete cervical SCI and 15 without SCI. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated by DTI for ventral horn and intermediate column of sacral cord at S2-S4 level. All participants underwent urodynamic examination. The urodynamic parameters (voiding efficiency (VE), and bladder contractility index (BCI)) and DTI parameters were compared between people with and without SCI. The correlations between DTI values (FA and ADC) and urodynamic parameters were analyzed. The FA values were significantly lower and the ADC values were significantly higher in the intermediate column and ventral horn at S2-S4 level of the participants with SCI compared with their able-bodied counterparts (p < 0.05). VE and BCI were significantly different between the two groups (p < 0.05). The FA values of intermediate column positively correlated with BCI (r = 0.749, p < 0.05) and the ADC values negatively correlated with BCI (r = -0.471, p < 0.05) in participants with SCI. The DTI values of sacral cord were not correlated with each urodynamic parameter in participants without SCI (p > 0.05). Complete cervical SCI might lead to microstructural changes of the sacral cord, which might further affect bladder contraction.

Early presentation of urinary retention in multiple system atrophy: can the disease begin in the sacral spinal cord?

Lower urinary tract (LUT) dysfunction presents early in multiple system atrophy (MSA), usually initially as urinary urgency, frequency and incontinence, and voiding difficulties/urinary retention becomes apparent over time. We have observed a subset of patients who instead presented initially with urinary retention requiring catheterisation. At presentation, these patients had only subtle neurological signs that would not fulfil the diagnostic criteria of MSA; however, the anal sphincter electromyography (EMG) was abnormal and they reported bowel and sexual dysfunction, suggesting localisation at the level of the sacral spinal cord. They subsequently developed classical neurological signs, meeting the diagnostic criteria for probable MSA. One patient was confirmed to have MSA at autopsy. We postulate that in a subset of patients with MSA, the disease begins in the sacral spinal cord and then spreads to other regions resulting in the classical signs of MSA. The transmissibility of alpha-synuclein has been demonstrated in animal models and the spread of pathology from sacral cord to other regions of the central nervous system is therefore plausible. Patients presenting with urinary retention and mild neurological features would be an ideal group for experimental trials evaluating neuroprotection in MSA

Rostral lumbar segments are the key controllers of hindlimb locomotor rhythmicity in the adult spinal rat.

The precise location and functional organization of the spinal neuronal locomotor-related networks in adult mammals remain unclear. Our recent neurophysiological findings provided empirical evidence that the rostral lumbar spinal cord segments play a critical role in the initiation and generation of the rhythmic activation patterns necessary for hindlimb locomotion in adult spinal rats. Since added epidural stimulation at the S1 segments significantly enhanced the motor output generated by L2 stimulation, these data also suggested that the sacral spinal cord provides a strong facilitory influence in rhythm initiation and generation. However, whether L2 will initiate hindlimb locomotion in the absence of S1 segments, and whether S1 segments can facilitate locomotion in the absence of L2 segments remain unknown. Herein, adult rats received complete spinal cord transections at T8 and then at either L2 or S1. Rats with spinal cord transections at T8 and S1 remained capable of generating coordinated hindlimb locomotion when receiving epidural stimulation at L2 and when ensembles of locomotor related loadbearing input were present. In contrast, minimal locomotion was observed when S1 stimulation was delivered after spinal cord transections at T8 and L2. Results were similar when the nonspecific serotonergic agonists were administered. These results demonstrate in adult rats that rostral lumbar segments are essential for the regulation of hindlimb locomotor rhythmicity. In addition, the more caudal spinal networks alone cannot control locomotion in the absence of the rostral segments around L2 even when loadbearing rhythmic proprioceptive afferent input is imposed.NEW & NOTEWORTHY The exact location of the spinal neuronal locomotor-related networks in adult mammals remains unknown. The present data demonstrate that when the rostral lumbar spinal segments (~L2) are completely eliminated in thoracic spinal adult rats, hindlimb stepping is not possible with neurochemical modulation of the lumbosacral cord. In contrast, eliminating the sacral cord retains stepping ability. These observations highlight the importance of rostral lumbar segments in generating effective mammalian locomotion.

Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury.

Spinal cord injury (SCI) usually affects younger age groups with male preponderance. The most common traumatic cause is road traffic accident followed by sports accidents and gun-shot injuries. Infections and vascular events make up non-traumatic causes. There is regional variance in incidence and prevalence of SCI. Most systematic reviews have been undertaken from USA, Canada, and Australia with only few from Asia with resultant difficulty in estimation of worldwide figures. Overall, the incidence varies from 12 to more than 65cases/million per year. The first peak is in young men between 15 and 29years and second peak in older adults. The average age at injury is 40years, with commonest injury being incomplete tetraplegia followed by complete paraplegia, complete tetraplegia, and incomplete paraplegia. The bladder function is reliant on both central and peripheral nervous systems for co-ordination of storage and voiding phases. The pathophysiology of bladder dysfunction can be described as an alteration in micturition reflex. It is postulated that a new spinal reflex circuit develops which is mediated by C fibers as response to reorganization of synaptic connections in spinal cord. This is responsible for the development of neurogenic detrusor overactivity (NDO). Various neurotrophic hormones like nerve growth factor affect the morphological and physiological changes of the bladder afferent neurons leading to neuropathic bladder dysfunction. A suprasacral SCI usually results in a voiding pattern consistent with NDO and sphincter dyssynergia. Injury to either the sacral cord or cauda equina results in detrusor hypoactivity/areflexia with sphincter weakness.

The Bulbocavernosus Reflex in the Differential Diagnosis of Multiple System Atrophy with Predominant Parkinsonism and Parkinson's Disease.

Multiple system atrophy with predominant parkinsonism (MSA-P) is a degenerative disorder that presents with autonomic dysfunction, atypical parkinsonism, and ataxia. Parkinson’s disease (PD) is an age-related neurological disorder of the central nervous system. Differentiation between MSA-P and PD is important because treatments, complications, and prognoses differ. The bulbocavernosus reflex (BCR) tests the afferent and efferent signals of the pudendal nerve as well as the sacral cord. In this study, we investigated differences in BCR parameters between MSA-P and PD patients. Thirty-eight MSA-P patients and 32 PD patients were selected to participate in our electrophysiological investigations. The Keypoint EMG/EP system was used to induce the BCR, and latencies and amplitudes were recorded for systematic statistical analyses. Area under the curve of the receiver operating characteristic was used to assess the specificity and sensitivity of the BCR parameters. A BCR was elicited in 76.32% of MSA-P patients and 93.75% of PD patients. The BCR latencies of the MSA-P group were longer than those of the PD group (p < 0.001). In addition, the MSA-P group had a lower BCR amplitude compared to the PD and control groups (p < 0.001). We discovered the difference between MSA-P and PD through BCR latencies and amplitudes. Compared to PD patients, MSA-P patients have longer latencies and lower amplitudes. Therefore, the BCR may be used to discriminate between MSA-P and PD in some cases.