Chronic Spinal Cord Injured Research Articles

Low-Dose LPS Modulates Microglia/Macrophages Phenotypic Transformation to Amplify Rehabilitation Effects in Chronic Spinal Cord Injured (CSCI) Mice.

Spinal cord injury (SCI) results in stalled motor function recovery under the chronic phase. One of the reasons due to the presence of ongoing inflammation. Therefore, regulating the status of immune cells may help reopen the window for neural repair, which represents a potential therapeutic target. In this study, we aimed to investigate whether this could be achieved in mice with cervical 5 crush CSCI (4W) by utilizing a concentration of 0.5mg/kg of lipopolysaccharide (LPS) to stimulate microglia/macrophages. Additionally, the mice underwent rehabilitation training for another 6 weeks. Our results showed that systemic injection of LPS enhanced the effects of forelimb rehabilitation training, as evaluated through single pellet grasping (SPG). Electrophysiological studies revealed the restoration of cortical drive to the injured side's forelimb muscles in the training combined with LPS group. Tract tracing studies demonstrated the reconstruction of cortical innervation to the cervical spinal cord. Furthermore, the levels of pro-inflammatory phenotype markers, such as inducible nitric oxide synthase (INOS) and CD68, decreased, while the expression of anti-inflammatory phenotype markers, including arginase 1 (ARG-1) and CD206, increased. Importantly, this phenotypic switch in microglia/macrophages was accompanied by an increase in phagocytic activity markers as indicated by BODIPY + IBA1 + staining. Collectively, our data suggests that low-dose LPS improves the effects of rehabilitation training by regulating the phenotypic transformation of microglia/macrophages in CSCI.This study provides a fresh perspective and intervention direction for the clinical treatment of chronic spinal cord injuries.

Clinical Guidelines of Patient-Centered Bladder Management of Neurogenic Lower Urinary Tract Dysfunction due to Chronic Spinal Cord Injury - Part 2

Bladder management of chronic spinal cord injured (SCI) patients usually starts with conservative treatment or minimally invasive procedures. This article reports the current evidence and expert opinions on the patient-centered bladder management of neurogenic lower urinary tract dysfunction (NLUTD) among patients with chronic SCI in Taiwan. We evaluated the role of clean intermittent catheterization (CIC), cystostomy, medical treatment, and minimally invasive therapy for treating urinary incontinence and voiding dysfunction in patients with chronic SCI. The bladder management for chronic SCI patients should be individualized. A balance between upper urinary tract protection and life quality improvement should be considered. Hand dexterity, abdominal muscle power, bladder sensation, and degree of urethral sphincter dyssynergia might affect the improvement of voiding efficiency and NLUTD. Intradetrusor Botulinum Toxin Type A (BoNT-A) injection has been proven to effectively treat neurogenic detrusor overactivity in SCI patients. However, CIC is still required in some patients after treatment. The urethral sphincter BoNT-ABoNT-A injection can effectively relax the dyssynergic sphincter; however, exacerbation of urinary incontinence usually limits its application in SCI patients. Repeat BoNT-ABoNT-A injection is necessary to maintain the therapeutic efficacy; therefore, some SCI patients might discontinue the treatment and convert to a permanent bladder management by surgical intervention. Identification of high-risk SCI patients is important to prevent renal functional deterioration in those with chronic SCI-NLUTD. Avoiding renal function deterioration and improving the quality of life of SCI patients with NLUTD are the most important aspects of treatment. Annual active surveillance of bladder and renal function is necessary.

Buprenorphine, a partial opioid agonist, prevents modulation of H-reflex induced by pulsed electromagnetic stimulation in spinal cord injured rats

Our recent study revealed that spinal electromagnetic stimulation (sEMS) applied at low (0.2 Hz) frequencies may improve diminished transmission in damaged spinal cord in spinal cord injured (SCI) rats. We have recently begun a pilot study investigating the effects of sEMS in non-injured and SCI humans. One unexpected result was the reduction of chronic low back pain (CLBP), reported by some patients following sEMS treatment. Chronic low back pain is one of the main causes of disability affecting the general population. Opioids are the most common drugs prescribed to US adults with CLBP. To optimize parameters for sEMS for pain treatment, in this study we used the SCI animal model and examined effects of sEMS applied at lumbosacral level on parameters and frequency-dependent depression (FDD) of Hoffmann H-reflex responses, known as common neurophysiological measures for evaluation of sensorimotor condition and plasticity in humans. We have also examined the interactive effects of sEMS and the opiate partial agonist Buprenorphine on the parameters of H-reflex in naïve and SCI rats. Consistent with previous reports, chronic SCI resulted in a marked decrease of threshold intensity required to evoke H-reflex and a lesser rate of FDD of the H-response in adult rats. Our current study revealed the optimum parameters of spinal EMS for best recovery of the properties of the H-reflex in chronic SCI animals. Here we demonstrate that electro-magnetic stimulation applied at spinal L4-L5 level with a pulsed mode (pulse at 20 Hz frequency for 5 sec with 25 sec break between pulses, total 40 trains for 20 min; PSEMS) reversed effects of SCI on key parameters of H-reflex: i.e. (1) restored the threshold intensity of electric current applied at tibial nerve to evoke the H-reflex and (2) recovered FDD properties of the H-reflex in SCI rats. Importantly, subcutaneous injections of Buprenorphine, prior to PSEMS administration, abolished the ability of PSEMS to recover both threshold intensity and FDD of the H-reflex in chronic SCI animals. These results suggest that a semi-synthetic opioid Buprenorphine and PSEMS might share common sites of action. We thus conclude that PSEMS might carry potential as a non-invasive treatment approach for chronic low back pain.

Recovery of motor function of chronic spinal cord injury by extracellular pyruvate kinase isoform M2 and the underlying mechanism

In our previous study, we found that pyruvate kinase isoform M2 (PKM2) was secreted from the skeletal muscle and extended axons in the cultured neuron. Indirect evidence suggested that secreted PKM2 might relate to the recovery of motor function in spinal cord injured (SCI) mice. However, in vivo direct evidence has not been obtained, showing that extracellular PKM2 improved axonal density and motor function in SCI mice. In addition, the signal pathway of extracellular PKM2 underlying the increase in axons remained unknown. Therefore, this study aimed to identify a target molecule of extracellular PKM2 in neurons and investigate the critical involvement of extracellular PKM2 in functional recovery in the chronic phase of SCI. Recombinant PKM2 infusion to the lateral ventricle recovered motor function in the chronic phase of SCI mice. The improvement of motor function was associated with axonal increase, at least of raphespinal tracts connecting to the motor neurons directly or indirectly. Target molecules of extracellular PKM2 in neurons were identified as valosin-containing protein (VCP) by the drug affinity responsive target stability method. ATPase activation of VCP mediated the PKM2-induced axonal increase and recovery of motor function in chronic SCI related to the increase in axonal density. It is a novel finding that axonal increase and motor recovery are mediated by extracellular PKM2-VCP-driven ATPase activity.

Detecting peripheral motor nervous system involvement in chronic spinal cord injury using two novel methods: MScanFit MUNE and muscle velocity recovery cycles

ObjectiveTo examine the peripheral nervous system (PNS) in spinal cord injured (SCI) patients using two novel methods: (1) MScanFit MUNE; a motor unit number estimation method detecting motor unit loss and (2) muscle velocity recovery cycles (MVRCs) measuring muscle membrane properties which has previously shown depolarization of the muscle membrane in denervated muscles. MethodsThirty chronic SCI patients (lesion above Th10) and twenty-five gender –and age matched healthy controls (HC) were examined. MScanFit was recorded from peroneal nerve to anterior tibial muscle (TA) and tibial nerve to abductor hallucis muscle after excluding localized mononeuropathies. MVRCs were recorded from TA. ResultsNerve conduction studies showed mononeuropathy in 8 patients (27%) (sciatic (2), -or peroneal nerve (6)). SCI patients had in average reduced motor unit number compared with HC and prolonged muscle refractory period and reduced supernormality. SignificanceA high prevalence of nerve lesion and a diffuse affection of the PNS following SCI are highly relevant findings that should be accounted for when planning neurorehabilitation for persons living with SCI.

Validation of the instrumented evaluation of spatio-temporal gait parameters in patients with motor incomplete spinal cord injury.

Observational, descriptive, transversal. To evaluate the validity and reliability of spatio-temporal gait parameters measured by GaitRite in motor incomplete spinal cord-injured (SCI) patients. National Institute of Rehabilitation, Mexico city. 23 motor subacute and chronic incomplete SCI American Spinal Cord Injury Association Impairment Scale (AIS) D subjects were measured. The 10-meter walking test (10 MWT), 6-minute walking test (6 MWT), Walking Index for Spinal Cord Injury II (WISCI-II), Spinal Cord Independence Measure III (SCIM-III) and the GaitRite evaluation were carried out concurrently in order to determine validity. The 10 MWT and GaitRite evaluation were performed at different occasions in order to determine test-retest reliability. GaitRite offers a valid and reliable way to measure the mobility, symmetry and stability characteristics of gait SCI subjects. GaitRite precision and sensitivity is approximately three times better than clinical tests. Clinical tests cannot address the stability properties of gait. Subjects' higher gait velocity is related to more independence (SCIM-III), lower use of walking aids (WISCI-II), better performance in lower extremities motor score (LEMS) and better gait's mobility. Spatio-temporal gait parameters measured by GaitRite are both valid and reliable. Further studies are necessary to establish sensitivity of the instrument.

Impaired toll like receptor-7 and 9 induced immune activation in chronic spinal cord injured patients contributes to immune dysfunction

Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction. We tested our hypothesis on healthy and chronic SCI patients with a level of injury above T-6. Donor PBMCs were isolated and stimulated with different toll like receptor ligands and T-cell inducers aiming to investigate whether chronic SCI patients display differential immune activation to multiple innate and adaptive immune cell stimulants. We demonstrate that SCI patients' B-cell and plasmacytoid dendritic cells retain their functionality in response to TLR7 and TLR9 ligand stimulation as they secreted similar levels of IL6 and IFNα. The immune dysfunction is not probably due to impaired T-cell function, since neither CD4+ T-cell dependent IFNγ producing cell number nor IL10 producing regulatory T-cells resulted different outcomes in response to PMA-Ionomycin and PHA-LPS stimulation, respectively. We showed that TLR7 dependent IFNγ and IP10 levels and TLR9 mediated APC function reduced substantially in SCI patients compared to healthy subjects. More importantly, IP10 producing monocytes were significantly fewer compared to healthy subjects in response to TLR7 and TLR9 stimulation of SCI PBMCs. When taken together this work implicated that these defects could contribute to persistent complications due to increased susceptibility to infections of chronic SCI patients.

Transcranial magnetic stimulation (TMS) responses elicited in hindlimb muscles as an assessment of synaptic plasticity in spino-muscular circuitry after chronic spinal cord injury

Electromagnetic stimulation applied at the cranial level, i.e. transcranial magnetic stimulation (TMS), is a technique for stimulation and neuromodulation used for diagnostic and therapeutic applications in clinical and research settings. Although recordings of TMS elicited motor-evoked potentials (MEP) are an essential diagnostic tool for spinal cord injured (SCI) patients, they are reliably recorded from arm, and not leg muscles. Mid-thoracic contusion is a common SCI that results in locomotor impairments predominantly in legs. In this study, we used a chronic T10 contusion SCI rat model and examined whether (i) TMS-responses in hindlimb muscles can be used for evaluation of conduction deficits in cortico-spinal circuitry and (ii) if plastic changes at spinal levels will affect these responses. In this study, plastic changes of transmission in damaged spinal cord were achieved by repetitive electro-magnetic stimulation applied over the spinal level (rSEMS). Spinal electro-magnetic stimulation was previously shown to activate spinal nerves and is gaining large acceptance as a non-invasive alternative to direct current and/or epidural electric stimulation. Results demonstrate that TMS fails to induce measurable MEPs in hindlimbs of chronically SCI animals. After facilitation of synaptic transmission in damaged spinal cord was achieved with rSEMS, however, MEPs were recorded from hindlimb muscles in response to single pulse TMS stimulation. These results provide additional evidence demonstrating beneficial effects of TMS as a diagnostic technique for descending motor pathways in uninjured CNS and after SCI. This study confirms the ability of TMS to assess plastic changes of transmission occurring at the spinal level.

Effects of pudendal neuromodulation on bladder function in chronic spinal cord-injured rats

Few studies have investigated the feasibility of using pudendal neuromodulation to regulate bladder function in spinal cord-injured (SCI) animals. The present study aimed to determine the effects of electrical activation of the pudendal sensory branch on improving voiding functions in rats 6 weeks after a spinal cord injury and to explore the underlying neuromodulatory mechanisms. Two urodynamic measurements were used to assess the effects of electrical stimulation (ES) on bladder and urethral functions: simultaneous recordings of the intravesical pressure (IVP) during continuous isotonic transvesical infusion (i.e., isotonic IVP) and external urethral sphincter (EUS) electromyography (EUS-EMG), and simultaneous recordings of transvesical pressure under isovolumetric conditions (i.e., isovolumetric IVP) and urethral perfusion pressure (UPP). Six weeks after the SCI, the rats showed voiding dysfunction, as indicated by abnormal cystometric measurements (e.g., increased volume threshold, increased contraction amplitude, and increased residual volume, and decreased voided volume). The voiding efficiency (VE) decreased to 13% after the SCI, but increased to 22-34% after applying pudendal afferent stimulation. In addition, pudendal stimulation significantly increased the EUS burst period and increased the difference between the UPP and the high-frequency oscillation (HFO) baselines, and changed the time offset between bladder and EUS activities. These findings suggest that pudendal afferent stimulation improved the VE by prolonging the micturition interval, decreased the urethral resistance, and recovered detrusor-sphincter dyssynergia during the voiding phase. This study demonstrates the feasibility of using pudendal neuromodulation in chronic SCI rats. These results could aid in developing an advanced neural prosthesis to restore bladder function in clinical settings.

Evaluation of serum myostatin and sclerostin levels in chronic spinal cord injured patients.

Case-control study. To assess serum myostatin levels, bone mineral density (BMD), appendicular skeletal muscle mass (ASMM) and serum sclerostin levels in chronic spinal cord injured (SCI) patients and healthy controls. SCI centre in Italy. Blood samples, whole-body bioelectrical impedance analysis and BMD measurement with the ultrasound technique at the calcaneus level were taken from patients suffering from chronic SCI (both motor complete and incomplete) and healthy control subjects. A total of 28 SCI patients and 15 healthy controls were enrolled. Serum myostatin levels were statistically higher (P<0.01) in SCI patients compared with healthy controls. Similar results were found comparing both the motor complete and the motor incomplete SCI subgroups to healthy controls. Serum sclerostin was significantly higher in patients with SCI compared with healthy controls (P<0.01). BMD, stiffness and mean T-score values in SCI patients were significantly lower than those in healthy controls. Serum myostatin concentrations in the motor complete SCI subgroups correlated only with serum sclerostin levels (r(2)=0.42; P=0.001) and ASMM (r(2)=0.70; P=0.002) but not in healthy controls. Serum myostatin and serum sclerostin are significantly higher in chronic SCI patients compared with healthy controls. They are potential biomarkers of muscle and bone modifications after SCI. This is the first study reporting an increase in serum myostatin in patients suffering from chronic SCI and a correlation with ASMM.

Preclinical evidence supporting the clinical development of central pattern generator-modulating therapies for chronic spinal cord-injured patients.

Ambulation or walking is one of the main gaits of locomotion. In terrestrial animals, it may be defined as a series of rhythmic and bilaterally coordinated movement of the limbs which creates a forward movement of the body. This applies regardless of the number of limbs—from arthropods with six or more limbs to bipedal primates. These fundamental similarities among species may explain why comparable neural systems and cellular properties have been found, thus far, to control in similar ways locomotor rhythm generation in most animal models. The aim of this article is to provide a comprehensive review of the known structural and functional features associated with central nervous system (CNS) networks that are involved in the control of ambulation and other stereotyped motor patterns—specifically Central Pattern Generators (CPGs) that produce basic rhythmic patterned outputs for locomotion, micturition, ejaculation, and defecation. Although there is compelling evidence of their existence in humans, CPGs have been most studied in reduced models including in vitro isolated preparations, genetically-engineered mice and spinal cord-transected animals. Compared with other structures of the CNS, the spinal cord is generally considered as being well-preserved phylogenetically. As such, most animal models of spinal cord-injured (SCI) should be considered as valuable tools for the development of novel pharmacological strategies aimed at modulating spinal activity and restoring corresponding functions in chronic SCI patients.

Dexmedetomidine for chronic spinal cord injured patient

To the Editor: Anesthesia for spinal cord injured (SCI) patients is challenging for anesthesiologists. Although many patients undergoing surgery below the injured spinal cord level can proceed without anesthesia, autonomic dysreflexia (AD) and spasms can occur, and patients often require adequate sedation and anxiolysis during the operation. AD can occur not only in patients with lesions above T6, but also in those with lower lesion levels [1]. Therefore, close monitoring and careful management is essential for SCI patients [2]. We experienced a case of a 66-year-old man with a history of paraplegia. He had lost sensory and motor response below the T7 level because of a traffic accident 40 years earlier. The patient preferred to be unconscious for surgery. After monitoring vital signs, dexmedetomidine was infused at a rate of 0.6 lg/kg/h for monitored anesthesia care (MAC). No AD or spasm symptoms occurred, and the patient’s BIS was maintained with moderate sedation (70–80). Open bladder stone removal was done successfully without anesthesia. Hypertensive crisis induced by AD is paroxysmal and may be dangerous. Patients with SCI are sensitive to circulating noradrenaline [2]. Dexmedetomidine, a highly selective a2-adrenergic agonist, reduces circulating catecholamines and results in sympatholysis, anxiolysis, and respiratory preservation [3]. Thus, dexmedetomidine can be used as a safe sedative agent during MAC in patients with chronic SCI.

Therapeutic outcome and patient adherence to repeated onabotulinumtoxinA detrusor injections in chronic spinal cord-injured patients and neurogenic detrusor overactivity

To investigate the continuous therapeutic effects and urinary incontinence severity after repeated detrusor injections of 200-U of onabotulinumtoxinA (BoNT-A) in chronic spinal cord-injured (SCI) patients. Between 2006 and 2010, patients with chronic SCI and refractory neurogenic detrusor overactivity (DO) were treated with repeated sets of 200-U BoNT-A injected into 20 sites every 6 months. All patients underwent urological examinations and video-urodynamic studies at baseline and after each BoNT-A treatment. The outcomes were measured using Urogenital Distress Inventory 6-item short form (UDI-6) for urinary incontinence. The severity of urinary incontinence and urodynamic parameters were compared after each BoNT-A injection. A total of 59 SCI patients with a mean age of 42.1±13.1 years were enrolled. The UDI-6 incontinence scores persistently improved for up to three injections. The rate of dryness and mild incontinence reported by patients persistently improved from 25.4% at baseline to 74% at 3 months after the fourth injection, but decreased slightly after the fourth injection. The overall satisfaction rate after single or repeated injections was 59.3% (35 patients), and the failure rate was 33.9% (20 patients), and discontinuation rate owing to adverse events (2 recurrent UTI, 2 autonomic dysreflexia) was 6.8% (4 patients). Among the 20 patients who reported failure to treatment, 10 patients (16.9%) reported no significant improvement after one or repeated injections, eight converted to augmentation enterocystoplasty. Repeated 200-U BoNT-A injections every 6 months for neurogenic DO in chronic SCI patients provided a satisfactory initial outcome. However, only 20% patients continued the repeated treatment.

Should sperm be cryopreserved after spinal cord injury?

AbstractIn spinal cord injured (SCI) patients, three main factors may cause infertility: erectile dysfunction, ejaculatory dysfunction and impaired semen quality. This letter aims to discuss how we can manage SCI patients’ fertility in accordance with patient-centred care. For such SCI patients aged 20 to 40, having children represents hope for the future. Furthermore, it is a way to rebuild a life after the spinal injury and must be seen as an important part of the rehabilitation program. We suggest that sperm cryopreservation may contribute to patient-centred care management of SCI patients’ fertility, although there is no scientific evidence that cryopreservation will improve fertility outcome after SCI. Indeed, sperm cryopreservation is an affordable and simple technique in specialised centres with trained staff. Here, a protocol to manage SCI patients’ fertility is discussed: we propose PVS for sperm banking to all SCI patients after the phase of spinal shock during the rehabilitation program. If live sperm are retrieved, they are frozen and stored; however, if no live sperm are retrieved, electroejaculation and/or surgical sperm extraction are proposed only for patients who desire biological fatherhood. Prospective studies on the evolution of semen parameters, ejaculatory dysfunction, post-infectious obstructions and spermatogenesis impairment in chronic SCI patients are urgently needed to provide robust data for the evidence-based management of SCI patients’ fertility. Even if use rates are expected to be low, sperm banking may be a simple and affordable preventative measure for selected male SCI patients.

Hemodynamic alterations and myocardial mitochondrial respiration in diabetic spinal cord injured rats

Spinal cord injured (SCI) individuals are at high risk for cardiovascular disease (CVD). The more severe a spinal cord injury, the greater risk of all CVD. In addition, SCI also increases the prevalence of disorders such as type II diabetes due to metabolic abnormalities. While higher risk of both diabetes and CVD may be associated with the immobility and increased sympathetic activation of patients with SCI, mitochondrial function may be affected by these factors thereby playing a role in decreasing cardiac efficiency. Mitochondrial function has been found to decrease in the spinal cord after SCI, but mitochondrial function in the heart is unknown due to limited research in cardiac dysfunction after SCI. We will use a rat model of spinal cord injury and type II diabetes to examine changes in CVD function. We expect to see decreased mitochondrial function that could explain the altered hemodynamics in the damaged heart of SCI diabetic animals. Not only will this study serve to assess the unique physiologic characteristics of the heart in chronic SCI individuals, but it will provide a different SCI model that incorporates diabetes for the purpose of exacerbating the onset of cardiovascular disease.

1647 STRIKING REDUCTION IN NEUROGENIC BLADDER DYSFUNCTION FOLLOWING REACTIVE OXYGEN SPECIES SCAVENGING IN THE LUMBOSACRAL SPINAL CORDS OF CHRONIC SPINAL CORD INJURED RATS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Neurogenic Voiding Dysfunction1 Apr 20121647 STRIKING REDUCTION IN NEUROGENIC BLADDER DYSFUNCTION FOLLOWING REACTIVE OXYGEN SPECIES SCAVENGING IN THE LUMBOSACRAL SPINAL CORDS OF CHRONIC SPINAL CORD INJURED RATS Matthew O. Fraser and Paul C. Dolber Matthew O. FraserMatthew O. Fraser Durham, NC More articles by this author and Paul C. DolberPaul C. Dolber Durham, NC More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1479AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Suprasacral spinal cord injury (SCI) results in bladder hyperreflexia characterized by low compliance and frequent high pressure, dyssynergic contractions. We hypothesize that spinal cord neurons involved in this hyperreflexic state exist as a phenotype and in a local environment consistent with central sensitization, including exposure to reactive oxygen species (ROS). Our experimental strategy was to determine whether scavenging ROS at the level of the lumbosacral spinal cord (LSSC) favorably affects the neural components of post-SCI neurogenic bladder behavior. To this end, continuous cystometry was performed in long term post-SCI rats before and after the ROS scavenger phenyl-N-tert-butylnitrone (PBN) was delivered directly to the LSSC. METHODS 18 female SD rats (225-250 g) underwent laminectomy and complete spinal cord transections at T10. At ≥4 weeks, the chronic SCI rats were anesthetized with isoflurane (0.4 %) and received an intrathecal (i.t.) catheter inserted at T10 with the tip at the L6 LSSC. Transvesical cystometry was performed under awake, restrained conditions (Ballman cage). Control cystometry was performed at a flow rate of 0.3 ml/min for >30 minutes to achieve a steady baseline. Rats were then given 3 i.t. doses of vehicle alone at 20-30 minute intervals prior to a single dose of 1 mg PBN in artificial cerebrospinal fluid (aCSF) (50 ul) and 10 ul of vehicle to clear dead space. Vehicle effects, if any, were stable by the third vehicle (V3), thus data following V3 were taken as control. All PBN data were analyzed by paired t-test from V3. RESULTS PBN resulted in a dramatic and significant (3X) increase in intermicturition interval, explainable by an increase in voiding efficiency (as evidenced by a >2X increase in voided volume together with a decrease in post-void intravesical pressure), together with an increase in compliance. Importantly, the number of non-voiding contractions decreased dramatically (to 26% of control values). CONCLUSIONS The effect of acute ROS inhibition at the LSSC produces a favorable response in chronic SCI rats, reducing many hallmark indices of neurogenic hyperreflexia secondary to traumatic suprasacral spinal cord injury. These results suggest that an ongoing activation of ROS production, likely due to central sensitization following suprasacral SCI, contributes significantly to the aberrant reflex activity associated with neurogenic bladder. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e665-e666 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Matthew O. Fraser Durham, NC More articles by this author Paul C. Dolber Durham, NC More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Plasticity of urinary bladder reflexes evoked by stimulation of pudendal afferent nerves after chronic spinal cord injury in cats

Bladder reflexes evoked by stimulation of pudendal afferent nerves (PudA-to-Bladder reflex) were studied in normal and chronic spinal cord injured (SCI) adult cats to examine the reflex plasticity. Physiological activation of pudendal afferent nerves by tactile stimulation of the perigenital skin elicits an inhibitory PudA-to-Bladder reflex in normal cats, but activates an excitatory reflex in chronic SCI cats. However, in both normal and chronic SCI cats electrical stimulation applied to the perigenital skin or directly to the pudendal nerve induces either inhibitory or excitatory PudA-to-Bladder reflexes depending on stimulation frequency. An inhibitory response occurs at 3–10 Hz stimulation, but becomes excitatory at 20–30 Hz. The inhibitory reflex activated by electrical stimulation significantly (P < 0.05) increases the bladder capacity to about 180% of control capacity in normal and chronic SCI cats. The excitatory reflex significantly (P < 0.05) reduces bladder capacity to about 40% of control capacity in chronic SCI cats, but does not change bladder capacity in normal cats. Electrical stimulation of pudendal afferent nerves during slow bladder filling elicits a large amplitude bladder contraction comparable to the contraction induced by distension alone. A bladder volume about 60% of bladder capacity was required to elicit this excitatory reflex in normal cats; however, in chronic SCI cats a volume less than 20% of bladder capacity was sufficient to unmask an excitatory response. This study revealed the co-existence of both inhibitory and excitatory PudA-to-Bladder reflex pathways in cats before and after chronic SCI. However our data combined with published electrophysiological data strongly indicates that the spinal circuitry for both the excitatory and inhibitory PudA-to-Bladder reflexes undergoes a marked reorganization after SCI.

Bladder and Sphincter Control after Spinal Cord Injury

A new neuroprosthesis to restore both continence and micturition was developed in chronic spinal cord injured (SCI) cats based on pudendal nerve stimulation and blockade. The present mini‐review summarizes our progress in the design and development of a new stimulation strategy to implement this new neuroprosthesis. Our studies showed that the pudendal‐to‐bladder spinal reflex could be either excitatory or inhibitory, depending on the frequency of pudendal nerve stimulation. High‐frequency biphasic electrical stimulation can reversibly block pudendal nerve conduction to suppress detrusor sphincter dyssynergia (DSD). By combining the different frequencies of pudendal nerve stimulation, both continence and micturition could be restored in chronic SCI cats, indicating the possibility that a successful clinical application of this new stimulation strategy might be achieved in the near future.

Bladder inhibition or excitation by electrical perianal stimulation in a cat model of chronic spinal cord injury

To test the hypothesis that perianal electrical stimulation (PES) in chronic spinal cord-injured (SCI) cats could induce frequency-dependent inhibitory or excitatory reflex bladder responses. The experiments were conducted > or =4-5 weeks after spinal cord transection at the T9-T10 level. PES was applied via a pair of hook electrodes to the perianal skin area in three awake female cats with chronic SCI. A double-lumen balloon catheter was inserted through the urethra into the bladder to monitor bladder pressure and infuse saline (2-4 mL/min). Under isovolumetric conditions PES at 3-10 Hz significantly inhibited large-amplitude reflex bladder activity induced by bladder distension above the micturition volume threshold. However, PES at 20-50 Hz induced large-amplitude bladder contractions when the bladder volume was below the micturition volume threshold. Inhibitory PES (7 Hz) significantly increased the mean (sem) bladder capacity by 40 (10)% when it was applied continuously during cystometrography. The optimum excitatory PES (30 Hz) induced large-amplitude (>25 cmH(2)O), long-duration (>20 s) bladder contractions at a wide range of bladder volumes (10-90% of bladder capacity). This study showed that activation of pudendal afferent fibres by PES could induce frequency-dependent reflex bladder responses in awake cats with chronic SCI, indicating that a possible noninvasive treatment based on PES could be developed to restore both continence and micturition function for patients with SCI.

Bladder inhibition or voiding induced by pudendal nerve stimulation in chronic spinal cord injured cats

To investigate pudendal-to-bladder spinal reflexes in chronic spinal cord injured (SCI) cats induced by electrical stimulation of the pudendal nerve. Bladder inhibition or voiding induced by pudendal nerve stimulation at different frequencies (3 or 20 Hz) was studied in three female, chronic SCI cats under alpha-chloralose anesthesia. Voiding induced by a slow infusion (2-4 ml/min) of saline into the bladder was very inefficient (voiding efficiency=7.3%+/-0.9%). Pudendal nerve stimulation at 3 Hz applied during the slow infusion inhibited reflex bladder activity, and significantly increased bladder capacity to 147.2+/-6.1% of its control capacity. When the 3-Hz stimulation was terminated, voiding rapidly occurred and the voiding efficiency was increased to 25.4+/-6.1%, but residual bladder volume was not reduced. Pudendal nerve stimulation at 20 Hz induced large bladder contractions, but failed to induce voiding during the stimulation due to the direct activation of the motor pathway to the external urethral sphincter. However, intermittent pudendal nerve stimulation at 20 Hz induced post-stimulus voiding with 78.3+/-12.1% voiding efficiency. The voiding pressures (39.3+/-6.2 cmH2O) induced by the intermittent pudendal nerve stimulation were higher than the voiding pressures (23.1+/-1.7 cmH2O) induced by bladder distension. The flow rate during post-stimulus voiding induced by the intermittent pudendal nerve stimulation was significantly higher (0.93+/-0.04 ml/sec) than during voiding induced by bladder distension (0.23+/-0.07 ml/sec). This study indicates that a neural prosthetic device based on pudendal nerve stimulation might be developed to restore micturition function for people with SCI.