Lumbosacral Cord Research Articles

Spinal glycinergic and gamma-aminobutyric acid-ergic neurons inhibit the micturition reflex after electrical stimulation of the perineum in rats with pelvic venous congestion.

To examine whether electrical stimulation of the perineum inhibited urinary frequency in rats with pelvic venous congestion, and whether electrical stimulation influences spinal glycinergic/gamma-aminobutyric acid-ergic neurons. Bilateral common iliac veins and bilateral uterine veins were ligated to create pelvic venous congestion rats. At 4weeks after ligation, cystometry was carried out before and after electrical stimulation with/without intrathecal injection of strychnine (a glycine receptor antagonist) and/or bicuculline (a gamma-aminobutyric acid typeA receptor antagonist). In addition, measurement of amino acid levels in the lumbosacral cord was carried out with/without electrical stimulation, and cystometry was carried out after oral administration of glycine. Continuous cystometry showed that the interval between bladder contractions was shorter in pelvic venous congestion rats than in sham rats. Electrical stimulation did not change cystometric parameters in sham rats, but the interval between bladder contractions was increased by electrical stimulation in pelvic venous congestion rats. Electrical stimulation increased the levels of glutamic acid, glycine, gamma-aminobutyric acid, and taurine in the lumbosacral cord of pelvic venous congestion rats. Intrathecal strychnine abolished the effects of electrical stimulation in pelvic venous congestion rats, and intrathecal administration of both strychnine and bicuculline shortened the interval between bladder contractions more than before electrical stimulation. Oral administration of glycine (3%) to pelvic venous congestion rats increased bladder capacity. Electrical stimulation of the perineum inhibits urinary frequency mainly through activation of spinal glycinergic neurons, and partly through activation of gamma-aminobutyric acid-ergic neurons in a rat model of pelvic venous congestion.

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.

Streptozotocin-induced diabetes causes upregulation of serotonin (5-HT)2A/C receptors in lumbosacral cord motoneurons and down regulation of serotonergic paraneurons in the urethra

Lower urinary tract (LUT) dysfunction is the most common complication of diabetes mellitus (DM). An involvement of the 5-HT2A receptor in spinal micturition control has been demonstrated in urethane anaesthetized DM rats in which i.v. administration of the 5-HT2A/2C receptor agonist 2,5-methoxy-4-iodoamphetamine (DOI), stimulated high frequency oscillations (HFOs) and improved micturition. However, the mechanisms involved in these effects are not completely understood. The present work showed that 5-HT2A and -2C receptors were upregulated in lumbosacral cord motoneurons, and the number of serotonergic paraneurons were downregulated in the urethra in DM group. The importance of the downregulation of urethral paraneurons in DM remains to be elucidated but may be related to the reduced urethral sensation caused by the disease. We suggest that targets of 5-HT receptor agonists for improvement of voiding function may be found both in the LUT and lumbosacral spinal cord.

The Ascending Reticular Activating System.

Discovery of the ascending reticular activating system (ARAS) can be attributed to work done in research neuroscientist Horace Magoun's laboratory. Before this finding, most scientists would focus on the diencephalon (and anterior midbrain) but not more caudally. Stimulation of the medial bulbar reticular formation in the pontine and midbrain tegmentum resulted disappearance of synchronized discharge and low-voltage fast activity. The effects were mediated by a thalamic projection system. This finding was a dramatic departure from the early philosophers' ascription of the awake soul to the ventricles (Galen), lumbosacral cord (Plato), pineal gland (Descartes), and even from more modern nineteenth- and twentieth-century hypotheses that the corpus striatum or periaqueductal gray matter housed the "seat of awareness." Magoun and his collaborators closed in on its true location in the cephalic brainstem-clinicians and neuropathologists would soon follow.

Effect of 5-HT2A receptor antagonist ketanserin on micturition in male rats

ObjectivesThis study aimed to investigate the effects of ketanserin on micturition mediated via the 5-HT2A receptor in the motoneuron nucleus of the Lumbosacral cord, as reflected in high frequency oscillations (HFOs) of intravesical pressure and the external urethral sphincter electromyogram (EUS-EMG) in anesthetized male rats. Methods：Male Sprague-Dawley rats were used. Cystometry and EUS-EMG were performed in all rats under urethane anesthesia to examine the variations after successive intrathecal (i.t.) administration of various doses of ketanserin into the lumbosacral cord. Immunofluorescence staining and Western blotting were made to observe the distribution of 5-HT2 A and −2C receptors in the lumbosacral cord motor neurons. ResultsCompared to the controls, ketanserin-treated rats showed a declined trend of dose-dependent manner in the HFOs, in accordance with the variation of EUS-EMG, while decreased micturition volume, voiding efficiency, and increased post-void residual volume was only observed at the dose of 0.1 mg/kg. The effects of ketanserin on the HFO and EUS-EMG activity were partially or completely reversed by the 5-HT2A/2C receptor agonist, DOI. Meanwhile, immunofluorescence staining and Western blot analysis showed that immunoreactivity of 5-HT2A receptor was higher than that of 5-HT2C, labeling in the lumbosacral cord motoneurons. ConclusionsThe intrathecally administrated 5-HT2A receptor antagonist ketanserin can weaken the EUS bursting activity, decrease HFOs, and reduce voiding efficiency as dose dependently. The effects of ketanserin on micturition may be mainly mediated via the 5-HT2A receptors in the motoneuron nucleus of the lumbosacral cord.

The serotonin (5-hydroxytryptamine) 5-HT7 receptor is up-regulated in Onuf's nucleus in rats with chronic spinal cord injury.

To examine the effect of intrathecal (i.t.) serotonin (5-hydroxytryptamine) 5-HT7 agonist administration on voiding function in the urethane-anesthetised rat, and the change in 5-HT7 receptor (5-HT7 R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). In all, 32 female Sprague-Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n=16 each). At 8weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5-HT7 R-selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1-30μg/kg) induced significant dose-dependent increases in micturition volume, voiding efficiency, number of high-frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non-voiding contractions. The 5-HT7 R antagonist, SB-269970 (10μg/kg), partially reversed LP44-induced changes. Using PRV retrograde tracing and immunofluorescence, 5-HT7 Rs were found in the L6-S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5-HT7 Rs in the ventral L6-S1 spinal cord in SCI rats. A 5-HT7 R agonist, given i.t., improved voiding efficiency in urethane-anesthetised SCI rats, and the 5-HT7 R was significantly up-regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5-HT7 R could be a target for therapeutic interventions.

PD36-01 THE 5-HT7 RECEPTOR IS UP-REGULATED IN ONUF'S NUCLEUC

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Neurogenic Voiding Dysfunction II1 Apr 2018PD36-01 THE 5-HT7 RECEPTOR IS UP-REGULATED IN ONUF'S NUCLEUC Jianshu Ni, Baojun Gu, nailong cao, and xiaohu wang Jianshu NiJianshu Ni More articles by this author , Baojun GuBaojun Gu More articles by this author , nailong caonailong cao More articles by this author , and xiaohu wangxiaohu wang More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1724AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It was previously reported that a 5-HT7 agonist, given intravenously, could enhance external urethral sphincter (EUS) activity and improve voiding efficiency after spinal cord injury (SCI). The present study examined the effect of intrathecal 5-HT7 agonist administration on voiding function, and the change of 5-HT7 receptor expression in lumbosacral cord Onuf's nucleus after SCI. METHODS Thirty-two female SD rats were divided into spinally intact (SI) group and SCI group (n=16 each). Eight weeks after transection, half of the rats underwent continuous cystometry under urethane anesthetization, and the 5-HT7 selective agonist LP44 was given intrathecally. Half of the remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence (IF) and Western Blot. RESULTS Intrathecally administered LP44 had no effect in spinally intact (SI) rats. In SCI rats, LP44 (1-30 ug/kg) induced significant dose-dependent increases in micturition volume, voiding efficiency, number of high-frequency oscillation (HFO) per micturition, and decrease in residual volume, bladder capacity, and peak bladder pressure. The 5-HT7 receptors antagonist, SB-269970 (10 ug/kg), partially reversed LP44-induced changes. By PRV retrograde tracing and IF, 5-HT7 receptors were demonstrated in L6-S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly stronger in SCI rats. Western blot showed a significant increase of 5-HT7 receptors in ventral L6-S1 spinal cord in SCI rats. CONCLUSIONS A 5-HT7 agonist, given intrathecally, improved voiding efficiency in SCI rats, and the 5-HT7 receptor was significantly up-regulated in lumbosacral cord Onuf's nucleus. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e726 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jianshu Ni More articles by this author Baojun Gu More articles by this author nailong cao More articles by this author xiaohu wang More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Lumbar to sacral root rerouting to restore bladder function in a feline spinal cord injury model: Urodynamic and retrograde nerve tracing results from a pilot study.

Lumbar to sacral rerouting surgery can potentially allow voiding via a skin-central nervous system-bladder reflex pathway. Here, we assessed if this surgery was effective in treating neurogenic bladder dysfunction/sphincter in felines. Eight cats underwent spinal cord transection (SCT) at thoracic level 10/11. Unilateral L7 to S1 ventral root anastomosis was performed 1 month later in six cats. Two cats served as transection-only controls. Electrical and manual stimulation of L6-S1 dermatomes, and urodynamics were performed at 3, 5, 7, and 9/10 months post transection. At 9/10 months, cats were also evaluated by direct electrophysiological testing of anastomosed roots with urodynamics, then tissue collection and examination of the root anastomosis site and lumbosacral cord ventral horns for cells retrogradely labeled from tracer dye injected 2 weeks earlier into the bladder wall. At 9/10 months, four of six rerouted cats exhibited increased detrusor pressure provoked by cutaneous stimulation, one cat bilaterally. Two cats presented with a voiding stream after ipsilateral cutaneous stimulation at 7 and 9 months. All six rerouted animals showed regrowth of axons from the L7 ventral horn to the bladder, although some aberrant axonal regrowth was also observed. L7 to S1 ventral root rerouting below the level of SCT showed successful axonal regrowth to the bladder from the L7 spinal cord segment in all rerouted animals, and induced increased detrusor pressure response to cutaneous stimulation in a subset. This feasibility study paves the way for future animal studies for bladder reinnervation.

A sexually dimorphic peptidergic system in the lower spinal cord controlling penile function in non-human primates.

Experimental animal study. Although a population of gastrin-releasing peptide (GRP) neurons in the lumbar spinal cord has an important role in erection and ejaculation in rats, little information exists on this GRP system in primates. To identify the male-specific GRP system in the primate spinal cord, we studied the lumbosacral cord in macaque monkeys as a non-human primate model. University laboratory in Japan. To determine the gene sequence of GRP precursors, the rhesus macaque monkey genomic sequence data were searched, followed by phylogenetic analysis. Subsequently, immunocytochemical analysis for GRP was performed in the monkey spinal cord. We have used bioinformatics to identify the ortholog gene for GRP precursor in macaque monkeys. Phylogenetic analysis suggested that primate prepro-GRP is separated from that of other mammalian species and clustered to an independent branch as primates. Immunocytochemistry for GRP further demonstrated that male-dominant sexual dimorphism was found in the spinal GRP system in monkeys as in rodents. We have demonstrated in macaque monkeys that the GRP system in the lower spinal cord shows male-specific dimorphism and may have an important role in penile functions not only in rodents but also in primates. Tissues of Nihonzaru (Japanese macaque monkeys) were provided in part by National Institutes of Natural Sciences (NINS) through the National Bio-Resource Project (NBRP) of the MEXT, Japan. This work was supported in part by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (to KT; 15KK0343, 15J40220 and HS; 15K15202, 15KK0257, 15H05724).

Chronic spinal cord injury causes upregulation of serotonin (5-HT)2A and 5-HT2C receptors in lumbosacral cord motoneurons.

To investigate whether the voiding dysfunction caused by spinal cord injury (SCI) in rats can be improved by i.v. administration of the serotonin (5-HT)2A/2C receptor agonist 2,5-dimethoxy-4-iodophenyl-2-aminopropanehydrochloride (DOI), and to discuss whether the mechanism can be ascribed to 5-HT2A and 5-HT 2C receptor upregulation in lumbosacral cord motoneurons. Female Sprague-Dawley rats were divided into two groups (SCI group vs normal control [NC] group). Under urethane anaesthesia, cystometry was performed to examine the variation in urodynamic variables before and after successive intrathecal (i.t.) administration of various doses of DOI into the lumbosacral cord. Changes in 5-HT2A and -2C receptors in the lumbosacral cord were also investigated using immunohistochemical staining and Western blot analysis. Compared with NC rats, the SCI rats had higher bladder capacity and post-void residual urine volume, and lower voiding efficiency. After SCI, DOI improved voiding efficiency, probably via external urethral sphincter (EUS) activity. Immunohistochemical staining and Western blot analysis showed that 5-HT2A and -2C receptors were upregulated in lumbosacral cord motoneurons. In rats with SCI, DOI can improve voiding efficiency; this may be attributable to 5-HT2A and -2C receptor upregulation in lumbosacral cord motoneurons controlling EUS activity.

Colokinetic effect of somatostatin in the spinal defecation center in rats.

Somatostatin and its receptors are expressed in the spinal cord, but the functional roles of the peptide remain unknown. In this study, we examined the colokinetic effect of somatostatin in the spinal defecation center in anesthetized rats. Intrathecal application of somatostatin into the lumbo-sacral cord caused propulsive contractions of the colorectum. However, somatostatin administered intravenously or intrathecally to the thoracic cord failed to enhance colorectal motility. Transection of the thoracic cord had no significant impact on the colokinetic action of somatostatin. The enhancement of colorectal motility by intrathecal administration of somatostatin was abolished by severing the pelvic nerves. Our results demonstrate that somatostatin acting on the spinal defecation center causes propulsive motility of the colorectum in rats. Considering that somatostatin is involved in nociceptive signal transmission in the spinal cord, our results provide a rational explanation for the concurrent appearance of chronic abdominal pain and colonic motility disorders in IBS patients.

Lumbosacral lipoma and low-lying cord with minimal deficits

Lumbosacral lipoma and low-lying cord with minimal deficits

Association of morphine-induced analgesic tolerance with changes in gene expression of GluN1 and MOR1 in rat spinal cord and midbrain.

We aimed to examine association of gene expression of MOR1 and GluN1 at mRNA level in the lumbosacral cord and midbrain with morphine tolerance in male Wistar rats. Analgesic effects of morphine administrated intraperitoneally at doses of 0.1, 1, 5 and 10 mg/kg were examined using a hot plate test in rats with and without a history of 15 days morphine (10 mg/kg) treatment. Morphine-induced analgesic tolerance was also assessed on days 1, 5, 10 and 15 of chronic morphine injections. Two groups with history of 15 days injections of saline or morphine (10 mg/kg) were decapitated on day 15 and their lumbosacral cord and midbrain were dissected for evaluating MOR1 and GluN1 gene expression. The results of the hot plate test showed that morphine (5 and 10 mg/kg) induced significant analgesia in naïve rats but its analgesic effects in rats receiving 15 days injections of morphine (10 mg/kg) was decreased, indicating tolerance to morphine analgesia. The results also showed that the GluN1 gene expression in tolerant rats was decreased by 71% in the lumbosacral cord but increased by 110 % in the midbrain compared to the control group. However, no significant change was observed for the MOR1 gene expression in both areas. It can be concluded that tolerance following administration of morphine (10 mg/kg) for 15 days is associated with site specific changes in the GluN1 gene expression in the spinal cord and midbrain but the MOR1 gene expression is not affected.

Gene Expression Profile of Calcium/Calmodulin-Dependent Protein Kinase IIα in Rat Spinal Cord and Midbrain During Induction of Morphine Analgesic Tolerance

Background: Calcium/calmodulin-dependent protein kinase IIα (CamKIIα) may modulate the function of mu-opioid receptors by phosphorylation and therefore, be involved in development of morphine-induced analgesic tolerance. Objectives: The current study aimed to examine changes in gene expression of CamKIIα in the lumbosacral cord and midbrain during induction of morphine analgesic tolerance. Materials and Methods: Male Wistar rats weighing 250 - 300 g were used. Two groups of rats (n = 6 per group) received saline (1 mL/kg) or morphine (10 mg/mL/kg) twice-daily for eight days, and induction of morphine analgesic tolerance was assessed using a hotplate test on days one, four and eight of the injections. The lumbosacral spinal cord and midbrain were also dissected in six independent groups (n = 4 per group) on days one, four and eight of saline or morphine injections to examine changes in gene expression of CamKIIα with a semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Results: The result of the hotplate test showed that the rats receiving repeated injections of morphine developed tolerance and exhibited significant decrease in antinociception on days four and eight of the injections compared to that of day one (P < 0.001). The result of gene expression in the lumbosacral cord showed no significant changes in the CamKIIα gene expression on days one and eight but its expression significantly increased by 102 % on day four of the injections (P < 0.01). In addition, the CamKIIα gene expression in the midbrain showed no significant changes on days one and four, but it significantly decreased by 67 % on day eight of morphine injection (P < 0.01). Conclusions: It can be concluded that changes in the CamKIIα gene expression in the lumbosacral cord and midbrain during repeated injections of morphine may be differently associated with induction of morphine tolerance.

Evaluation of lumbar enlargement motor neuron excitability: Comparison between H-reflex and transcutaneous spinal cord stimulation

Multisegmental muscle responses (MMR) are reflexes in the leg muscles evoked by transcutaneous electrical spinal cord stimulation over the Th11–Th12 vertebrae. We have used MMR to evaluate the excitability of lumbosacral motor neurons in individuals having paraplegia of low limbs. Ten individuals were tested using H-reflexes and MMR bilaterally before (n0 = 20) and during 4-weeks course of rehabilitation (n=76). The H-reflex and MMR of m. gastrocnemius lateralis were obtained in: 15 and 13 cases out of 20, respectively. Both reflexes were recorded in 11 and were absent in 3 cases, matched up to 70% of recordings. In dynamic, the both methods were 100% reproducible and the responses’ amplitude varied in similar directions in 67% of records. The data confirm the validity and reproducibility of the MMR for evaluation of the motor neurons excitability in lumbosacral cord. The H-reflex magnitude shows moderate correlation with MMR in m. gastrocnemius lateralis (r = 0.59, p < 0.001), and weak correlation with MMR in mm. rectus femoris, biceps femoris, and tibialis anterior (r < 0.40, p < 0.001). These findings do not allow extrapolate the results from the H-reflex measurement on the state of lumbosacral cord on the whole. At the same time, measurements of the MMR allow estimate simultaneously the excitability of motor pools innervating several muscle groups. This gives the possibility to assess the functional state of the motor neurons in the lumbosacral cord for clinical and experimental studies, including the spinal cord damage.

Hypothesis: Hughlings Jackson and presynaptic inhibition: is there a big picture?

Presynaptic inhibition is a very powerful inhibitory mechanism and, despite many detailed studies, its purpose is still only partially understood. One accepted function is that, by reducing afferent inflow to the spinal cord and brainstem, the tonic level of presynaptic inhibition prevents sensory systems from being overloaded. A corollary of this function is that much of the incoming sensory data from peripheral receptors must be redundant, and this conclusion is reinforced by observations on patients with sensory neuropathies or congenital obstetric palsy in whom normal sensation may be preserved despite loss of sensory fibers. The modulation of incoming signals by presynaptic inhibition has a further function in operating a "gate" in the dorsal horn, thereby determining whether peripheral stimuli are likely to be perceived as painful. On the motor side, the finding that even minimal voluntary movement of a single toe is associated with widespread inhibition in the lumbosacral cord points to another function for presynaptic inhibition: to prevent reflex perturbations from interfering with motor commands. This last function, together with the normal suppression of muscle and cutaneous reflex activity at rest, is consistent with Hughlings Jackson's concept of evolving neural hierarchies, with each level inhibiting the one below it.

MP68-20 LUMBAR TO SACRAL ROOT REROUTING TO RESTORE VOIDING FUNCTION IN A FELINE SPINAL CORD INJURY MODEL: URODYNAMIC AND RETROGRADE NERVE TRACING RESULTS FROM A PILOT STUDY

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology II1 Apr 2016MP68-20 LUMBAR TO SACRAL ROOT REROUTING TO RESTORE VOIDING FUNCTION IN A FELINE SPINAL CORD INJURY MODEL: URODYNAMIC AND RETROGRADE NERVE TRACING RESULTS FROM A PILOT STUDY Ornella Lam van ba, Mary F. Barbe, Romain Caremel, Shachar Aharony, Oleg Loutochin, Line Jacques, Matthew Woods, Gerald F. Tuite, Michael R. Ruggieri, Lysanne Campeau, and Jacques Corcos Ornella Lam van baOrnella Lam van ba More articles by this author , Mary F. BarbeMary F. Barbe More articles by this author , Romain CaremelRomain Caremel More articles by this author , Shachar AharonyShachar Aharony More articles by this author , Oleg LoutochinOleg Loutochin More articles by this author , Line JacquesLine Jacques More articles by this author , Matthew WoodsMatthew Woods More articles by this author , Gerald F. TuiteGerald F. Tuite More articles by this author , Michael R. RuggieriMichael R. Ruggieri More articles by this author , Lysanne CampeauLysanne Campeau More articles by this author , and Jacques CorcosJacques Corcos More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1357AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Following complete spinal cord injury (SCI), lumbar to sacral rerouting surgery has the potential to allow voiding via a new skin-central nervous system-bladder reflex pathway. We aimed to assess whether this surgery is effective in treating neurogenic bladder in a feline SCI model METHODS Eight cats underwent SCT at T9-T10. Unilateral L7-S1 ventral root anastomosis was performed 1 month later in 6 cats. Remaining dorsal and ventral roots below L7 were transected, bilaterally. Bladders were checked three times per day and emptied with the Crede maneuver. The new neurological pathway was evaluated at 3, 5, 7 and 9 months by electrical and manual cutaneous stimulation of L7 dermatomes and urodynamics. At 9 months, cats were euthanized 2 weeks after bladder wall Fluorogold retrograde tracer injection and an assessor-blinded pathological exam of the L7-S1 root anastomosis site and lumbosacral cord ventral horns for presence of Fluorogold labeled cell bodies was performed. Outcomes included: 1) urodynamic responses to cutaneous or electrical stimulation the L7 dermatome 2) axonal growth from L7 and S1 ventral horns to the bladder; and 3) incidence of bladder hypertrophy RESULTS At 9 months, 3 of the 6 rerouted cats exhibited increased detrusor pressure provoked by unilateral cutaneous stimulation, and one cat bilaterally. Ipsilateral cutaneous stimulation produced a voiding stream in 2 cats. SCI controls did not respond. Mean bladder volume or weight was not different between rerouted animals and SCI controls. Postmortem studies determined the anastomosed ventral roots were one-sided L7 to S1 (3 right-sided rerouting and 3 left-sided). One right-rerouted cat also showed the left L7 ventral root was annealed to the right S1 root. Although some aberrant axonal regrowth was observed, all 6 rerouted animals showed regrowth of axons from the L7 ventral horn segment to the bladder using retrograde tracing, (Figure 1) including the animal with bilateral input to S1 CONCLUSIONS L7-to-S1 ventral root rerouting surgery below the level of SCT showed successful axonal regrowth to the bladder in all rerouted animals and induced urodynamic responses to cutaneous stimulation in a subset. This feasibility study paves the way for future studies for bladder re-innervation © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e897 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Ornella Lam van ba More articles by this author Mary F. Barbe More articles by this author Romain Caremel More articles by this author Shachar Aharony More articles by this author Oleg Loutochin More articles by this author Line Jacques More articles by this author Matthew Woods More articles by this author Gerald F. Tuite More articles by this author Michael R. Ruggieri More articles by this author Lysanne Campeau More articles by this author Jacques Corcos More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Prolonged central sensory conduction time in patients with chronic arsenic exposure

BackgroundMany patients from Toroku, Japan, who have chronic arsenic exposure demonstrate whole-body sensory disturbance that is slightly more pronounced in the extremities. Although previous research in this population showed a mild peripheral neuropathy, it is unknown whether these patients have central nervous system impairment. To investigate the lesion sites underlying sensory disturbance related to chronic arsenic poisoning, we analyzed somatosensory evoked potentials (SEP). MethodsClinical features, nerve conduction study results, and median and/or tibial SEP were analyzed in patients with chronic arsenic exposure (total, 13 patients; median & tibial, 4; median, 5; tibial, 4) retrospectively. The SEP findings in patients were compared with those in normal controls. ResultsThe median SEP results indicated a conduction delay between the proximal brachial plexus and the primary sensory cortex, and tibial SEP findings indicated a delay between the dorsal gray matter of the lumbosacral cord and the primary sensory cortex. ConclusionThis is the first study to identify an impairment of the central somatosensory pathway in patients with chronic arsenic exposure. Sensory disturbance in these patients is related not only to peripheral neuropathy but also to impairment of the central nervous system.

Dopamine is produced in the rat spinal cord and regulates micturition reflex after spinal cord injury

Dopamine (DA) neurons in the mammalian central nervous system are thought to be restricted to the brain. DA-mediated regulation of urinary activity is considered to occur through an interaction between midbrain DA neurons and the pontine micturition center. Here we show that DA is produced in the rat spinal cord and modulates the bladder reflex. We observed numerous tyrosine hydroxylase (TH)+ neurons in the autonomic nuclei and superficial dorsal horn in L6–S3 spinal segments. These neurons are dopamine-β-hydroxylase (DBH)− and some contain detectable dopamine decarboxylase (DDC), suggesting their capacity to produce DA. Interestingly, following a complete thoracic spinal cord injury (SCI) to interrupt supraspinal projections, more TH+ neurons emerged in the lumbosacral spinal cord, coincident with a sustained, low level of DA expression there and a partially recovered micturition reflex. Non-selective blockade of spinal DA receptors reduced bladder activity whereas activation of spinal D2-like receptors increased bladder activity and facilitated voiding. Additionally, depletion of lumbosacral TH+ neurons with 6-hydroxydopamine (6-OHDA) decreased bladder non-voiding contractions and voiding efficiency. Furthermore, injecting the transsynaptic neuronal tracer pseudorabies virus (PRV) into the bladder detrusor labeled TH+ cells in the lumbosacral cord, confirming their involvement in spinal micturition reflex circuits. These results illustrate that DA is synthesized in the rat spinal cord; plasticity of lumbosacral TH+ neurons following SCI may contribute to DA expression and modulate the spinal bladder reflex. Thus, spinally-derived DA and receptors could be a novel therapeutic target to improve micturition recovery after SCI.

Propiverine increases urethral wall catecholamine levels and bladder leak point pressure in rats.

To investigate whether propiverine has a noradrenaline re-uptake inhibitor and whether it acts on the lumbosacral cord or the urethral wall. In addition, we aimed to examine the effect of propiverine on leak point pressure in rats. A total of 72 female and 30 male rats were used to examine the following: (i) the change of leak point pressure caused by intravenous agents in rats with vaginal distention; (ii) the change of leak point pressure caused by intrathecal agents in rats with vaginal distention; (iii) the noradrenaline re-uptake inhibitor action of propiverine; and (iv) catecholamine levels in the bladder wall, urethral wall, cerebrospinal fluid and plasma after oral administration of propiverine. Intravenous injection of propiverine, imipramine and duloxetine increased the leak point pressure in rats with vaginal distention. Intrathecal naftopidil decreased the leak point pressure, whereas subsequent intravenous propiverine restored the leak point pressure to the level before intrathecal naftopidil in rats with vaginal distention. Propiverine acted like a noradrenaline re-uptake inhibitor, increasing noradrenaline and/or dopamine levels in the plasma, cerebrospinal fluid, and urethral wall perfusion fluid. Propiverine inhibits noradrenaline re-uptake, as well as having antimuscarinic and Ca-antagonist actions. The inhibition of noradrenaline re-uptake by propiverine mainly occurs at the urethral level and partially in the central nervous system, and might stimulate the smooth muscle of the bladder neck and proximal urethra through α1-adrenergic receptors, as well as stimulating the striated muscle of the urethra and pelvic floor by activation of spinal motoneurons. Therefore, propiverine might be effective for both stress and urge incontinence.