S1 Ventral Roots Research Articles

Extradural contralateral S1 nerve root transfer for spastic lower limb paralysis.

The current study aims to ascertain the anatomical feasibility of transferring the contralateral S1 ventral root (VR) to the ipsilateral L5 VR for treating unilateral spastic lower limb paralysis. Six formalin-fixed (three males and three females) cadavers were used. The VR of the contralateral S1 was transferred to the VR of the ipsilateral L5. The sural nerve was selected as a bridge between the donor and recipient nerve. The number of axons, the cross-sectional areas and the pertinent distances between the donor and recipient nerves were measured. The extradural S1 VR and L5 VR could be separated based on anatomical markers of the dorsal root ganglion. The gross distance between the S1 nerve root and L5 nerve root was 31.31 (± 3.23) mm in the six cadavers, while that on the diffusion tensor imaging was 47.51 (± 3.23) mm in 60 patients without spinal diseases, and both distances were seperately greater than that between the outlet of S1 from the spinal cord and the ganglion. The numbers of axons in the S1 VRs and L5 VRs were 13 414.20 (± 2 890.30) and 10 613.20 (± 2 135.58), respectively. The cross-sectional areas of the S1 VR and L5 VR were 1.68 (± 0.26) mm 2 and 1.08 (± 0.26) mm 2, respectively. In conclusion, transfer of the contralateral S1 VR to the ipsilateral L5 VR may be an anatomically feasible treatment option for unilateral spastic lower limb paralysis.

Penile Erection Induced by Stimulation of Sacral S1/S2 Spinal Root in Cats

ObjectiveThis study aimed at determining whether stimulation of sacral spinal roots can induce penile erection in cats. Materials and MethodsIn anesthetized cats, a 20-gauge catheter was inserted into the corpus cavernosum to measure the penile pressure. Stimulus pulses (5–80 Hz, 0.2 ms) were applied through bipolar hook electrodes to sacral ventral roots alone or to combined ventral and dorsal roots of a single S1–S3 segment to induce penile pressure increases and penile erection. ResultsStimulation of the S1 or S2 ventral root at 30 to 40 Hz induced observable penile erection with rigidity and the largest increase (169 ± 11 cmH2O) in penile pressure. Continuous stimulation (10 minutes) of afferent and efferent axons by simultaneous stimulation of the S1 or S2 dorsal and ventral roots at 30 Hz also produced a large increase (190 ± 8 cmH2O) in penile pressure that was sustainable during the entire stimulation period. After a complete spinal cord transection at the T9–T10 level, simultaneous stimulation of the S1 or S2 dorsal and ventral roots induced large (186 ± 9 cmH2O) and sustainable increases in penile pressure. ConclusionThis study indicates the possibility to develop a novel neuromodulation device to restore penile erection after spinal cord injury using a minimally invasive surgical approach to insert a lead electrode through the sacral foramen to stimulate a sacral spinal root.

Defecation induced by stimulation of sacral S2 spinal root in cats.

The aim of this study was to determine whether stimulation of sacral spinal nerve roots can induce defecation in cats. In anesthetized cats, bipolar hook electrodes were placed on the S1-S3 dorsal and/or ventral roots. Stimulus pulses (1-50 Hz, 0.2 ms) were applied to an individual S1-S3 root to induce proximal/distal colon contractions and defecation. Balloon catheters were inserted into the proximal and distal colon to measure contraction pressure. Glass marbles were inserted into the rectum to demonstrate defecation by videotaping the elimination of marbles. Stimulation of the S2 ventral root at 7 Hz induced significantly (P < 0.05) larger contractions (32 ± 9 cmH2O) in both proximal and distal colon than stimulation of the S1 or S3 ventral root. Intermittent (5 times) stimulation (1 min on and 1 min off) of both dorsal and ventral S2 roots at 7 Hz produced reproducible colon contractions without fatigue, whereas continuous stimulation of 5-min duration caused significant fatigue in colon contractions. Stimulation (7 Hz) of both dorsal and ventral S2 roots together successfully induced defecation that eliminated 1 or 2 marbles from the rectum. This study indicates the possibility to develop a novel neuromodulation device to restore defecation function after spinal cord injury using a minimally invasive surgical approach to insert a lead electrode via the sacral foramen to stimulate a sacral spinal root.NEW & NOTEWORTHY This study in cats determined the optimal stimulation parameters and the spinal segment for sacral spinal root stimulation to induce colon contraction. The results have significant implications for design of a novel neuromodulation device to restore defecation function after spinal cord injury (SCI) and for optimizing sacral neuromodulation parameters to treat non-SCI people with chronic constipation.

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

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

Anatomical Feasibility of Extradural Transferring S2 and S3 Ventral Roots to S1 Ventral Root for Restoring Neurogenic Bladder in Spinal Cord Injury.

Anatomic study in six formalin-fixed cadavers. To determine the anatomical feasibility of transferring the S2 and S3 ventral roots (VRs) to S1 VR as a method for restoring bladder dysfunction in spinal cord injury. A large quantity of researches of neuroanastomosis methods have been used for treating the bladder dysfunction in spinal cord injury. However, some limitations retard the development of those studies. In this study, six formalin-fixed cadavers (four males, two females) were dissected. The feasibility of exposing the S1, S2, and S3 extradural nerve roots by the limited laminectomy, isolating the VR and dorsal roots from each extradural nerve root and transferring the S2,S3 VRs to the S1 VR were assessed. The pertinent distances and the nerve cross-sectional areas in each specimen were measured. The morphology of each nerve root was observed by hematoxylin-eosin staining. The limited laminectomy was performed to expose the S1 to S3 extradural nerve roots. The VRs could be isolated from each extradural nerve root at the location of the dorsal root ganglion and the hematoxylin-eosin staining showed that there were some connective tissues separating the VRs from the corresponding dorsal root ganglion. The S2 and S3 VRs have sufficient lengths to be transferred to S1 VR without grafting. The mean cross-sectional area of the S1 VR was 2.60 ± 0.17 mm, and that was 1.02 ± 0.32 mm and 0.51 ± 0.21 mm of the S2 and S3 VRs, respectively. This study demonstrated that use of the S2 and S3 VRs for extradural transfer to S1 VR for restoring bladder dysfunction is surgically feasible. 5.

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.

Effect of FK1706 on nerve regeneration after end-to-side neurorrhaphy of autonomic nerve and somatic nerve in rats

Objective To evaluate the effect of FK1706 on nerve regeneration after end-to-side (ETS) neurorrhaphy of autonomic nerve and somatic nerve in rats through morphological observation. Methods Thirty rats were randomly divided into three groups in terms of different treatments (n=10 in each group). In FK1706 group, the left L6 ventral root (L6VR) and L4 ventral root (L4VR) of rats were sutured in an ETS fashion and FK1706 (0.3 mg/kg) was administrated subcutaneously for 5 consecutive days per week for a total of 8 weeks after ETS neurorrhaphy. In ETS group, the same operation as FK1706 group was performed but without FK1706 applied after surgery. In control group, left L6 dorsal root (L6DR), S1 ventral root (S1VR) and S1 dorsal root (S1DR) were transected but the left L6VR was preserved as normal control. After 4 months, the left pelvic parasympathetic nerve (PPN) to which L6VR extended was harvested for semithin and ultrathin sections in FK1706 and ETS groups to count the number of myelinated axons. The number and morphology of myelinated axons and thickness of myelin sheath were compared between the two groups. Results After 4 months, the morphology of the regenerated L6VR distal to the neurorrhaphy site in FK1706 and ETS groups was normal. The number of regenerated myelinated axons of PPN was 515.6±43.3 and 328.4±46.4 in FK1706 and ETS groups, respectively (P=0.000). The thickness of myelin sheath of regenerated PPN was (0.672 4±0.110 1) μm and (0.466 8±0.076 3) μm in FK1706 and ETS groups, respectively (P=0.000). Conclusion The effect of autonomic nerve regeneration could be enhanced after ETS neurorrhaphy of autonomic nerve and somatic nerve through FK1706, which could improve rehabilitation of nerve injury. Key words: FK1706; Nerve regeneration; Autonomic nerve; Somatic nerve; End-to-side neurorrhaphy

Plasticity of Select Primary Afferent Projections to the Dorsal Horn after a Lumbosacral Ventral Root Avulsion Injury and Root Replantation in Rats.

Injuries to the conus medullaris and cauda equina portions of the spinal cord result in neurological impairments, including paralysis, autonomic dysfunction, and pain. In experimental studies, earlier investigations have shown that a lumbosacral ventral root avulsion (VRA) injury results in allodynia, which may be ameliorated by surgical replantation of the avulsed ventral roots. Here, we investigated the long-term effects of an L6 + S1 VRA injury on the plasticity of three populations of afferent projections to the dorsal horn in rats. At 8 weeks after a unilateral L6 + S1 VRA injury, quantitative morphological studies of the adjacent L5 dorsal horn showed reduced immunoreactivity (IR) for the vesicular glutamate transporter, VGLUT1 and isolectin B4 (IB4) binding, whereas IR for calcitonin gene-related peptide (CGRP) was unchanged. The IR for VGLUT1 and CGRP as well as IB4 binding was at control levels in the L5 dorsal horn at 8 weeks following an acute surgical replantation of the avulsed L6 + S1 ventral roots. Quantitative morphological studies of the L5 dorsal root ganglia (DRGs) showed unchanged neuronal numbers for both the VRA and replanted series compared to shams. The portions of L5 DRG neurons expressing IR for VGLUT1 and CGRP, and IB4 binding were also the same between the VRA, replanted, and sham-operated groups. We conclude that the L5 dorsal horn shows selective plasticity for VGLUT1 and IB4 primary afferent projections after an L6 + S1 VRA injury and surgical repair.

The feasibility study of extradural nerve anastomosis technique for canine bladder reinnervation after spinal cord injury

Objective: Intradural nerve anastomosis for bladder innervation has been demonstrated to be useful. However, its clinical application remains limited because of the complex surgery, its complications and extensive bony destruction. The purpose of the current study was to demonstrate the feasibility of extradural spinal root anastomosis for bladder innervation in canines.Methods: Ten beagle dogs were used. The length of the extradural segment of the nerve root, upper nerve root outlet (the point at which it emerges from the spinal dura mater) to S2 (dS2), the S3 (dS3) nerve root outlet distance, and the diameters of the extradural spinal roots were measured. The numbers of nerve fibers from L6 to S3 ventral roots were calculated using immunohistochemical staining.Results: The extradural spinal roots could be divided into a ventral root (VR) and a dorsal root (DR) before the ganglionic enlargement of the dorsal root, and the extradural motor nerve roots situate ventrally to their corresponding sensory nerve roots. The extradural nerve root lengths of S1 and parts of L7 were longer than the corresponding dS2. The numbers of nerve and motor nerve fibers, and the diameters of extradural nerve roots, were gradually descending from L6 to S3.Conclusion: The S1 VRs and parts of the L7 VRs can be extradurally anastomosed to the S2 nerves without tension. A nerve graft was needed for extradural anastomosis of L6 VRs and parts of L7 VRs to S2 VRs. This study demonstrated the feasibility of extradural spinal nerve anastomosis for treating neurogenic bladder in canines.

Reconstruction of atonic bladder innervation after spinal cord injury: A bladder reflex arc with afferent and efferent pathways

BackgroundEstablishing bladder reflex arcs only with the efferent pathway to induce micturition after spinal cord injury (SCI) has been successful. However, the absence of sensory function and micturition desires can lead to serious complications.ObjectivesTo reconstruct a bladder reflex arc with both afferent and efferent pathways to achieve atonic bladder innervation after SCI.MethodsA reflex arc was established by microanastomosis of the S2 dorsal root to the peripheral process of the L5 dorsal ganglion and the L5 ventral root to the S2 ventral root. The functions of the reflex arc were evaluated using electrophysiology, wheat germ agglutinin–horseradish peroxidase (WGA–HRP) tracing, and calcitonin gene-related peptide (CGRP) immunocytochemistry analysis. Hind-paw motion was evaluated by CatWalk gait.ResultsCompound action potentials and compound muscle action potentials were recorded at the right L5 dorsal root following electrical stimulation of right S2 dorsal root. Similar to the control side, these were not significantly different before or after the spinal cord destruction between L6 and S4. WGA–HRP tracing and CGRP immunocytochemistry showed that construction of the afferent and efferent pathways of the bladder reflex arc encouraged axonal regeneration of motor and sensory nerves, which then made contact with the anterior and posterior horns of the spinal cord, ultimately reestablishing axoplasmic transportation. Gait analysis showed that at 3 months following the operation, only the regularity index was significantly different as compared with 1 day before the operation, other parameters showing no difference.ConclusionBladder reflex arc with the afferent and efferent pathways reconstructs the micturition function without great influence on the motion of leg.

Extradural Nerve Anastomosis Technique for Bladder Reinnervation in Spinal Cord Injury

An anatomic study of extradural spinal root in 9 embalmed cadavers. To ascertain the anatomical parameters of the extradural spinal root and to demonstrate the feasibility of spinal root anastomoses without opening the spinal dura mater. Intradural anastomosis of the spinal root has made breakthrough progress in treating neurogenic bladder in spinal cord injury. However, because of the complex surgical procedures and extensive bony destruction, its clinical use is not widely promoted. Nine formalin-fixed cadavers were used. The distance between the nerve root outlet and ganglion center, the neighboring nerve root-outlet distance, and the gross anatomy of the extradural spinal root were measured with a surgical microscope. The number of nerve fibers from the T7 to S4 ventral roots (VRs) was calculated by immunohistochemical staining. The longest and shortest lengths of the extradural spinal root were observed at the S4 and T7 levels, with average values of 33.29 and 6.06 mm, respectively. The longest distance between the adjacent nerve root outlets was observed at L1-L2 (mean, 29.16 mm), and shortest at S3-S4 (mean, 11.79 mm). After leaving the dural sac, the spinal root descends in the spinal canal until reaching the corresponding intervertebral foramina, and the motor nerve roots still lie ventrally to the sensory nerve roots. The largest and smallest numbers of nerve fibers were observed at the L3 and S4 levels (mean, 9169 and 1356, respectively). The dorsal roots and VRs can both be successfully harvested and identified outside the dural sac. The S1 VR can be anastomosed to the S2 VR extradurally without nerve grafts. For extradural neuroanastomosis of the thoracic VRs to the S2 VR, a nerve graft is required. In addition, there are a sufficient number of nerve fibers for functional bladder recovery at the T7-T12 and S1 levels. This study supports the feasibility of extradural spinal root anastomosis as a modified surgical method for treating neurogenic bladder. N/A.

The diameters and number of nerve fibers in spinal nerve roots

ObjectiveTo investigate the anatomical and histological features of spinal nerve roots and provide base data for neuroanastomosis therapy for paraplegia.MethodsSpinal nerve roots from C1 to S5 were exposed on six adult cadavers. The diameter and the number of nerve fibers of each nerve root were measured, respectively, with a caliper and image analysis software.ResultsAs for ventral roots, the diameter of C5 (2.50 ± 0.55 mm) was the largest in cervical segments. In thoracic and lumbosacral segments, the diameter gradually increased from T11 to S1 and then decreased from S1 to S5 except L3. S1 (1.43 ± 0.16 mm) was the thickest root and S5 (0.14 ± 0.02 mm) was the thinnest one. As for dorsal roots, the diameter of C7 (4.61 ± 0.87 mm) was the largest in cervical segments. From T11 to S1, the diameter increased and then decreased gradually from S1 to S5. The diameter of dorsal roots from T1 to S5 was largest at S1 (2.95 ± 0.57 mm) and smallest at S5 (0.27 ± 0.13 mm), respectively. C7 (8467 ± 1019), T12 (6538 ± 892), L3 (9169 ± 1160), and S1 (8253 ± 1419) ventral roots contained the most nerve fibers in cervical, thoracic, lumbar, and sacral segments, respectively. Similarly, C7 (39 653 ± 8458), T1 (26 507 ± 7617), L5 (34 455 ± 2740), and S1 (41 543 ± 3036) dorsal roots, respectively, contained the most nerve fibers in their corresponding segments.ConclusionThe findings in the current study provided the imperative data and may be valuable for spinal nerve root microanastomosis surgery in the paraplegic patients.

Long-term effects of a lumbosacral ventral root avulsion injury on axotomized motor neurons and avulsed ventral roots in a non-human primate model of cauda equina injury

Here, we have translated from the rat to the non-human primate a unilateral lumbosacral injury as a model for cauda equina injury. In this morphological study, we have investigated retrograde effects of a unilateral L6–S2 ventral root avulsion (VRA) injury as well as the long-term effects of Wallerian degeneration on avulsed ventral roots at 6–10months post-operatively in four adult male rhesus monkeys.Immunohistochemistry for choline acetyl transferase and glial fibrillary acidic protein demonstrated a significant loss of the majority of the axotomized motoneurons in the affected L6–S2 segments and signs of an associated astrocytic glial response within the ventral horn of the L6 and S1 spinal cord segments. Quantitative analysis of the avulsed ventral roots showed that they exhibited normal size and were populated by a normal number of myelinated axons. However, the myelinated axons in the avulsed ventral roots were markedly smaller in caliber compared to the fibers of the intact contralateral ventral roots, which served as controls. Ultrastructural studies confirmed the presence of small myelinated axons and a population of unmyelinated axons within the avulsed roots. In addition, collagen fibers were readily identified within the endoneurium of the avulsed roots.In summary, a lumbosacral VRA injury resulted in retrograde motoneuron loss and astrocytic glial activation in the ventral horn. Surprisingly, the Wallerian degeneration of motor axons in the avulsed ventral roots was followed by a repopulation of the avulsed roots by small myelinated and unmyelinated fibers. We speculate that the small axons may represent sprouting or axonal regeneration by primary afferents or autonomic fibers.

Transfer of normal S1 nerve root to reinnervate atonic bladder due to conus medullaris injury

Neurogenic bladder dysfunction after spinal cord injury (SCI) is a major medical and social problem. In this study we assessed the effectiveness of neurogenic bladder reinnervation in patients with SCI using a normal S1 nerve root. Nine patients with bladder dysfunction caused by injury to the low conus medullaris (S2-S5) underwent a novel surgical procedure in which the unilateral proximal end of the S1 ventral root (VR) was anastomosed to the distal end of the S2 and S3 VRs. Seven patients regained satisfactory bladder control within 8-12 months after VR microanastomosis. The average residual urine volume decreased from 186.0 ± 35.0 ml to 43.0 ± 10.0 ml, and no urinary infections occurred. These results suggest the effectiveness of bladder innervation by S1 nerve transfer, which could provide a new approach for the reconstruction of atonic bladder function caused by low conus medullaris injuries.

Serotonergic 5-HT1A receptor agonist (8-OH-DPAT) ameliorates impaired micturition reflexes in a chronic ventral root avulsion model of incomplete cauda equina/conus medullaris injury

Trauma to the thoracolumbar spine commonly results in injuries to the cauda equina and the lumbosacral portion of the spinal cord. Both complete and partial injury syndromes may follow. Here, we tested the hypothesis that serotonergic modulation may improve voiding function after an incomplete cauda equina/conus medullaris injury. For this purpose, we used a unilateral L5–S2 ventral root avulsion (VRA) injury model in the rat to mimic a partial lesion to the cauda equina and conus medullaris. Compared to a sham-operated series, comprehensive urodynamic studies demonstrated a markedly reduced voiding efficiency at 12weeks after the VRA injury. Detailed cystometrogram studies showed injury-induced decreased peak bladder pressures indicative of reduced contractile properties. Concurrent external urethral sphincter (EUS) electromyography demonstrated shortened burst and prolonged silent periods associated with the elimination phase. Next, a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), was administered intravenously at 12weeks after the unilateral L5–S2 VRA injury. Both voiding efficiency and maximum intravesical pressure were significantly improved by 8-OH-DPAT (0.3–1.0mg/kg). 8-OH-DPAT also enhanced the amplitude of EUS tonic and bursting activity as well as duration of EUS bursting and silent period during EUS bursting. The results indicate that 8-OH-DPAT improves voiding efficiency and enhances EUS bursting in rats with unilateral VRA injury. We conclude that serotonergic modulation of the 5-HT1A receptor may represent a new strategy to improve lower urinary tract function after incomplete cauda equina/conus medullaris injuries in experimental studies.

Selective plasticity of primary afferent innervation to the dorsal horn and autonomic nuclei following lumbosacral ventral root avulsion and reimplantation in long term studies

Previous studies involving injuries to the nerves of the cauda equina and the conus medullaris have shown that lumbosacral ventral root avulsion in rat models results in denervation and dysfunction of the lower urinary tract, retrograde and progressive cell death of the axotomized motor and parasympathetic neurons, as well as the emergence of neuropathic pain. Root reimplantation has also been shown to ameliorate several of these responses, but experiments thus far have been limited to studying the effects of lesion and reimplantation local to the lumbosacral region. Here, we have expanded the region of investigation after lumbosacral ventral root avulsion and reimplantation to include the thoracolumbar sympathetic region of the spinal cord. Using a retrograde tracer injected into the major pelvic ganglion, we were able to define the levels of the spinal cord that contain sympathetic preganglionic neurons innervating the lower urinary tract. We have conducted studies on the effects of the lumbosacral ventral root avulsion and reimplantation models on the afferent innervation of the dorsal horn and autonomic nuclei at both thoracolumbar and lumbosacral levels through immunohistochemistry for the markers calcitonin gene-related peptide (CGRP) and vesicular glutamate transporter 1 (VGLUT1). Surprisingly, our experiments reveal a selective and significant decrease of CGRP-positive innervation in the dorsal horn at thoracolumbar levels that is partially restored with root reimplantation. However, no similar changes were detected at the lumbosacral levels despite the injury and repair targeting efferent neurons, and being performed at the lumbosacral levels. Despite the changes evident in the thoracolumbar dorsal horn, we find no changes in afferent innervation of the autonomic nuclei at either sympathetic or parasympathetic segmental levels by CGRP or VGLUT1. We conclude that even remote, efferent root injuries and repair procedures can have an effect on remote and non-lesioned sensory systems sharing common peripheral ganglia.

Micturition reflex arc reconstruction including sensory and motor nerves after spinal cord injury: Urodynamic and electrophysiological responses

ObjectiveTo evaluate artificial reflex arcs for micturition using urodynamics and electrophysiological recordings.DesignSixteen beagles were equally and randomly divided into two groups.MethodsIn group A, anastomosis of the proximal end of the left L7 ventral root (VR) and distal end of the left S2 VR was performed, as well as anastomosis of the L7 dorsal root (DR) and S2 DR to reconstruct the sensory and the motor function of the bladder. In group B the proximal end of the left L7 VR and the distal end of the left S2 VR were anastomosed, while the left L7 DR was kept intact to reconstruct the motor function of the bladder. Outcome measures included electrophysiological testing and the urodynamic measures. In addition, we also monitored urinary infection rates.ResultsStimulation to the left S2 DR in groups A and B both elevated the bladder pressure before and after the spinal lower motor neuron lesion. Single stimulation of the two groups both elicited evoked action potentials. Urinary infections occurred in group A (three occurrences) and in group B (eight occurrences) during the 3 months after the spinal lower motor neuron lesion.ConclusionData showed that both reconstructive methods could induce bladder micturition and evoked action potentials. However, in group A the micturition response was better and the urinary infection rates were lower after the spinal lower motor neuron lesion. Thus, the artificial physiological reflex arc reconstruction method used in group A, with sensory input above the lesion, might provide a better alternative in clinical practice.

Cauda Equina Repair in the Rat: Part 2. Time Course of Ventral Root Conduction Failure

Treatment for cauda equina (CE) ventral root injury is currently limited. Furthermore, relatively little is known about the time course of nerve root functional degeneration after such injury has occurred. Using a previously developed method for identifying spinal nerve roots that innervate the rat tail, we transected S2, S3, and S4 ventral roots and measured their ability to activate tail muscles out to 72 h post-injury by way of stimulus-evoked electromyography (EMG) recording. Immediately following transection, all distal ventral root stumps successfully activated muscles in the tail upon stimulation with no change in stimulus threshold (0.07±0.04 to 0.07±0.06 V using 0.1-msec pulse duration; 0.04±0.02 to 0.04±0.02 V using 1.0-msec pulse duration). Thresholds increased incrementally at each later time point (24 h: 0.27±0.33 V using 0.1-msec pulse duration; 0.09±0.07 V using 1-msec pulse duration; 48 h: 0.57±1.00 V using 0.1-msec pulse duration; 0.56±1.09 V using 1-msec pulse duration), with the first complete absence of EMG noted at 48 h post-transection in a subset of nerve roots (4/12). We were not able to elicit EMG at 72 h post-transection without moving distally along the nerve root stump. Based on neurofilament staining, only 51% of axons were identifiably intact nearest the site of injury at 24 h post-injury. This percentage dropped to 39% at 48 h, and just 18% at 72 h. Moving 5 mm from the site of injury, we identified 83% intact axons at 24 h post-transection, 77% at 48 h, and 68% at 72 h. Regenerative implications aside, if electrophysiological mapping of injured nerve roots is to be carried out for repair purposes, the rapid nature of conduction failure needs to be considered.

Spinal P2X receptor modulates muscle pressor reflex via glutamate

Static contraction of skeletal muscle evokes reflex increases in blood pressure and heart rate. Previous studies showed that P2X receptors located at the dorsal horn of the spinal cord play a role in modulating the muscle pressor reflex. P2X stimulation can alter release of the excitatory amino acid, glutamate (Glu). In this report, we tested the hypothesis that stimulation of P2X receptors enhances the concentrations of Glu ([Glu]) in the dorsal horn, and that blocking P2X receptors attenuates contraction-induced Glu increases and the resultant reflex pressor response. Contraction was elicited by electrical stimulation of the L(7) and S(1) ventral roots of 14 cats. Glu samples were collected from microdialysis probes inserted in the L(7) level of the dorsal horn of the spinal cord, and dialysate [Glu] was determined using the HPLC method. First, microdialyzing alpha,beta-methylene ATP (0.4 mM) into the dorsal horn significantly increased [Glu]. In addition, contraction elevated [Glu] from baseline of 536 +/- 53 to 1,179 +/- 192 nM (P < 0.05 vs. baseline), and mean arterial pressure by 39 +/- 8 mmHg in the control experiment. Microdialyzing the P2X receptor antagonist pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (10 mM) into the dorsal horn attenuated the contraction induced-Glu increase (610 +/- 128 to 759 +/- 147 nM; P > 0.05) and pressor response (16 +/- 3 mmHg, P < 0.05 vs. control). Our findings demonstrate that P2X modulates the cardiovascular responses to static muscle contraction by affecting the release of Glu in the dorsal horn of the spinal cord.

Bypassing Spinal Cord Injury: Surgical Reconstruction of Afferent and Efferent Pathways to the Urinary Bladder after Conus Medullaris Injury in a Rat Model

Afferent and efferent nerve function in the atonic bladder caused by conus medullaris injury in a rat model was established by intradural microanastomosis of the left L5 ventral root (VR) to right S2 VR to restore pure motor-to-motor reinnervation coupled with extradural postganglionic spinal nerve transfer of L5 dorsal root (DR) to S2 DR for pure sensory-to-sensory reinnervation. Early function of the reflex arc was evaluated by electrophysiological study, as well as by intravesicular pressure measurement and histological examination. The results demonstrated that single focal stimulation of the left S2 DR elicited evoked potentials at the left vesicular plexus before and after horizontal spinal cord damage between the L6 and S4 level. Bladder contraction was successfully initiated by trains of stimuli targeting the left L5-S2 DR anastomosis. Achievable bladder pressures and amplitude of bladder smooth muscle complex action potentials were unchanged before and after induced paraplegia and comparable to those of the control. Prominent axonal sprouting was seen in the distal part of nerve graft. Both afferent and efferent nerve pathways in the atonic bladder can be reconstructed by suprasacral motor-to-motor and sensory-to-sensory nerve transfer after spinal cord injury in rats. This reconstructive strategy has significant potential in clinical application.