Skin and not dorsal root stimulation reduces hypertonus in thoracic motor complete spinal cord injury: a single case report.

On demand and localized treatment for excessive muscle tone after spinal cord injury (SCI) is currently not available. Here, we examine the reduction in leg hypertonus in a person with mid-thoracic, motor complete SCI using a commercial transcutaneous electrical stimulator (TES) applied at 50 or 150 Hz to the lower back and the possible mechanisms producing this bilateral reduction in leg tone. Hypertonus of knee extensors without and during TES, with both cathode (T11-L2) and anode (L3-L5) placed over the spinal column (midline, MID) or 10 cm to the left of midline (lateral, LAT) to only active underlying skin and muscle afferents, was simultaneously measured in both legs with the pendulum test. Spinal reflexes mediated by proprioceptive (H-reflex) and cutaneomuscular reflex (CMR) afferents were examined in the right leg opposite to the applied LAT TES. Hypertonus disappeared in both legs but only during thoracolumbar TES, and even during LAT TES. The marked reduction in tone was reflected in the greater distance both lower legs first dropped to after being released from a fully extended position, increasing by 172.8% and 94.2% during MID and LAT TES, respectively, compared with without TES. Both MID and LAT (left) TES increased H-reflexes but decreased the first burst, and lengthened the onset of subsequent bursts, in the cutaneomuscular reflex of the right leg. Thoracolumbar TES is a promising method to decrease leg hypertonus in chronic, motor complete SCI without activating spinal cord structures and may work by facilitating proprioceptive inputs that activate excitatory interneurons with bilateral projections that in turn recruit recurrent inhibitory neurons.NEW & NOTEWORTHY We present proof of concept that surface stimulation of the lower back can reduce severe leg hypertonus in a participant with motor complete, thoracic spinal cord injury (SCI) but only during the applied stimulation. We propose that activation of skin and muscle afferents from thoracolumbar transcutaneous electrical stimulation (TES) may recruit excitatory spinal interneurons with bilateral projections that in turn recruit recurrent inhibitory networks to provide on demand suppression of ongoing involuntary motoneuron activity.

A Multielectrode Nerve Cuff for Chronic Velocity Selective Recording in a sheep model.

Supra-sacral spinal cord injury (SCI) causes loss of bladder fullness sensation and bladder over-activity, leading to retention and incontinence respectively. Velocity selective recording (VSR) of nerve roots innervating the bladder might enable identification of bladder activity. A 10-electrode nerve cuff for sacral nerve root VSR was developed and tested in a sheep model during acute surgeries and chronic implantation for 6 months. The cuff performed well, with 5.90±1.90 kΩ electrode, and <~800 Ω tissue impedance after 189 days implantation with a stable device and tissues. This is important information for assessing the feasibility of chronic VSR.Clinical Relevance-This demonstrates the manufacturing and performance of a neural interface for chronic monitoring of bladder nerve afferents with applications in urinary incontinence and retention management following SCI.

Upper limb neurodynamic mobilization disperses intraneural fluid in cervical nerve roots: A human cadaveric investigation.

BACKGROUND: Cervical radiculopathy is a common cause of neck pain with resultant intraneural edema and impaired nerve function. One strategy to treat radiculopathy is neurodynamic mobilization (NDM); however, little is known about the effect of this treatment on nerve tissue fluid dynamics. OBJECTIVE: Investigate the impact of upper limb, median nerve-biased NDM on longitudinal intraneural fluid dispersion in the C5,C6,C7 nerve roots in un-embalmed cadavers. DESIGN: In situ repeated measures. METHODS: Human cadavers (n = 8) were dissected to expose and inject C5,C6,C7 cervical nerve roots with a dying agent. Initial longitudinal dye spread was recorded after dye spread stabilization. Cadavers were taken through 150 repetitions of upper limb, median nerve-biased NDM followed by dye spread re-measurement. Paired-samples t-tests with Bonferroni correction (α = 0.017) were used to compare pre-vs post-NDM dye spread measurements at C5,C6,C7 nerve roots; a one-way repeated measures ANOVA (α = 0.05) was used to examine differences between change scores for C5,C6,C7 nerve roots. RESULTS: Median nerve-biased NDM resulted in significant intraneural longitudinal dye spread at C5 and C6 nerve roots of 0.6 ± 0.6 mm and 3.4 ± 3.9 mm, respectively (p < 0.014). Dye spread was not significant at C7 nerve root (0.4 ± 0.7 mm). There was no between root difference in change of longitudinal dye spread between C5, C6, and C7 nerve roots. CONCLUSIONS: The results of this study show median nerve-biased NDM produced internal fluid movement within C5 and C6 cervical nerve roots. Results provide insight regarding possible mechanism of action and feasibility of NDM in treatment of patients with cervical radiculopathy.

Passive limb training modulates respiratory rhythmic bursts.

Exercise modifies respiratory functions mainly through the afferent feedback provided by exercising limbs and the descending input from suprapontine areas, two contributions that are still underestimated in vitro. To better characterize the role of limb afferents in modulating respiration during physical activity, we designed a novel experimental in vitro platform. The whole central nervous system was isolated from neonatal rodents and kept with hindlimbs attached to an ad-hoc robot (Bipedal Induced Kinetic Exercise, BIKE) driving passive pedaling at calibrated speeds. This setting allowed extracellular recordings of a stable spontaneous respiratory rhythm for more than 4 h, from all cervical ventral roots. BIKE reversibly reduced the duration of single respiratory bursts even at lower pedaling speeds (2 Hz), though only an intense exercise (3.5 Hz) modulated the frequency of breathing. Moreover, brief sessions (5 min) of BIKE at 3.5 Hz augmented the respiratory rate of preparations with slow bursting in control (slower breathers) but did not change the speed of faster breathers. When spontaneous breathing was accelerated by high concentrations of potassium, BIKE reduced bursting frequency. Regardless of the baseline respiratory rhythm, BIKE at 3.5 Hz always decreased duration of single bursts. Surgical ablation of suprapontine structures completely prevented modulation of breathing after intense training. Albeit the variability in baseline breathing rates, intense passive cyclic movement tuned fictive respiration toward a common frequency range and shortened all respiratory events through the involvement of suprapontine areas. These observations contribute to better define how the respiratory system integrates sensory input from moving limbs during development, opening new rehabilitation perspectives.

Using a high-frequency carrier does not improve comfort of transcutaneous spinal cord stimulation.

Objective.Spinal cord neuromodulation has gained much attention for demonstrating improved motor recovery in people with spinal cord injury, motivating the development of clinically applicable technologies. Among them, transcutaneous spinal cord stimulation (tSCS) is attractive because of its non-invasive profile. Many tSCS studies employ a high-frequency (10 kHz) carrier, which has been reported to reduce stimulation discomfort. However, these claims have come under scrutiny in recent years. The purpose of this study was to determine whether using a high-frequency carrier for tSCS is more comfortable at therapeutic amplitudes, which evoke posterior root-muscle (PRM) reflexes.Approach.In 16 neurologically intact participants, tSCS was delivered using a 1 ms long monophasic pulse with and without a high-frequency carrier. Stimulation amplitude and pulse duration were varied and PRM reflexes were recorded from the soleus, gastrocnemius, and tibialis anterior muscles. Participants rated their discomfort during stimulation from 0 to 10 at PRM reflex threshold.Main Results.At PRM reflex threshold, the addition of a high-frequency carrier (0.87 ± 0.2) was equally comfortable as conventional stimulation (1.03 ± 0.18) but required approximately double the charge to evoke the PRM reflex (conventional: 32.4 ± 9.2µC; high-frequency carrier: 62.5 ± 11.1µC). Strength-duration curves for tSCS with a high-frequency carrier had a rheobase that was 4.8× greater and a chronaxie that was 5.7× narrower than the conventional monophasic pulse, indicating that the addition of a high-frequency carrier makes stimulation less efficient in recruiting neural activity in spinal roots.Significance.Using a high-frequency carrier for tSCS is equally as comfortable and less efficient as conventional stimulation at amplitudes required to stimulate spinal dorsal roots.

Human dental pulp stem cell monolayer and spheroid therapy after spinal motor root avulsion in adult rats.

Spinal cord injuries result in severe neurological deficits and neuronal loss, with poor functional recovery. Mesenchymal stem cells have shown promising results; therefore the present objective of this work was to compare motor recovery after treatment with human dental pulp stem cells (hDPSC) cultivated in monolayer (2D) or as spheroids (3D), following avulsion and reimplantation of spinal motor roots in adult rats. Thus, 72 adult female Lewis rats were divided into 4 groups: avulsion (AV); avulsion followed by reimplantation (AR); avulsion associated with reimplant and 2D cell therapy (AR + 2D), and avulsion associated with reimplant and 3D cell therapy (AR + 3D). The application of the cells in 2D and 3D was performed by microsurgery, with subsequent functional assessment using a walking track test (Catwalk system), immunohistochemistry, neuronal survival, and qRT-PCR in 1-, 4-, and 12-weeks post-injury. The animals in the AR + 2D and AR + 3D groups showed the highest neuronal survival rates, and immunofluorescence revealed downregulation of GFAP, and Iba-1, with preservation of synaptophysin, indicating a reduction in glial reactivity, combined with the maintenance of pre-synaptic inputs. There was an increase in anti-inflammatory (IL-4, TGFß) and a reduction of pro-inflammatory factors (IL-6, TNFα) in animals treated with reimplantation and hDPSC. As for the functional recovery, in all analyzed parameters, the AR + 2D group performed better and was superior to the avulsion alone. Overall, our results indicate that the 2D and 3D cell therapy approaches provide successful immunomodulation and motor recovery, consistent with advanced therapies after spinal cord injury.

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

OBJECTIVE: This study aimed at determining whether stimulation of sacral spinal roots can induce penile erection in cats. MATERIALS AND METHODS: In 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. RESULTS: Stimulation 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. CONCLUSION: This 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.

Correlation of age and the diameter of the cervical nerve roots C5 and C6 during the first 2 years of life analyzed by high-resolution ultrasound imaging.

AIM: To analyze the increase in diameter of the nerve roots C5 and C6 in early childhood. METHODS: The nerve roots of 56 children aged 0 days to 10 years (47 younger than 2 years) were examined by high-resolution ultrasound imaging. The correlation of diameter and age was statistically tested and a logarithmic regression analysis was performed to develop a logarithmic growth model. RESULTS: The increase in nerve root diameter is greatest during the first 2 years of life and then the growth rate decreases steadily. The relationship between age and diameter follows a logarithmic curve (p < 10-8 ). INTERPRETATION: The main increase in the diameter of the nerve roots happens in the first 2 years of life. Comparing data from a previous study, our data also suggest that the maturation of the proximal part of the median nerve is comparable to the maturation of its distal segments. This suggests a synchronous maturation of the axons and myelin sheath for the whole extent of the nerve, from the radix to its very distal part. WHAT THIS PAPER ADDS: Normative values for the size of the cervical nerve roots C5 and C6; an insight into the maturation of the proximal parts of the peripheral nervous system; and the correlation between age and cervical root diameter.

Dorsal root ganglia, neural crest migration, and spinal cord form in snakes.

The classic view of the vertebrate dorsal root ganglion is that it arises from trunk neural crest cells that migrate to positions lateral to the spinal cord, sending axons dorsally into the spinal cord and dendrites ventrally to meet with motor axons in the ventral root to form spinal nerves. As a result, the ganglion ends up lying in the dorsal root of the spinal nerve. Serial histological sections of parts of the trunk of juveniles of different snake species revealed that the ganglia lie distal to the junction of dorsal and ventral roots of spinal nerves and outside the neural canal. The anatomical position of spinal ganglia in snakes suggests that regulation of trunk neural crest migration in snakes differs from that in the model endotherms in which it has been most thoroughly explored. Dorsal roots have no distinct rootlets and the span of root entry to the spinal cord is short compared to that of ventral rootlets in the same segment. Comparing early developmental stages to juvenile spinal cords shows an increased separation of spinal nerve root sites and ventral migration of the ganglion in later development. Dorsal rami of the spinal nerves leave directly from the dorsal edge of the ganglion, and the ventral ramus leaves from the ventral tip of the ganglion. How these features relate to the developmental regulation of ganglion form and position and the extraordinary locomotor capabilities of the snake trunk are unclear.

Lateralization of bladder function in normal female canines.

This study aimed to identify potential lateralization of bladder function. Electrical stimulation of spinal roots or the pelvic nerve's anterior vesical branch was performed bilaterally in female dogs. The percent difference between the left and right stimulation-induced increased detrusor pressure was determined. Bladders were considered left or right-sided if differences were greater or less than 25% or 10%. Based on differences of 25%, upon stimulation of spinal roots, bladders were left-sided in 17/44 (38.6%), right-sided in 12/44 (27.2%) and bilateral in 15/44 (34.2%). Using ± 10%, 48% had left side dominance (n = 21/44), 39% had right side dominance (n = 17/44), and 14% were bilateral (n = 6/44). With stimulation of the pelvic nerve's anterior vesical branch in 19 dogs, bladders were left-sided in 8 (42.1%), right-sided in 6 (31.6%) and bilateral in 5 (26.3%) using 25% differences and left side dominance in 8 (43%), right sided in 7 (37%) and bilateral in 4 (21%) using 10% differences. These data suggest lateralization of innervation of the female dog bladder with left- and right-sided lateralization occurring at similar rates. Lateralization often varied at different spinal cord levels within the same animal.

The use of a detailed video-based locomotor pattern analysis system to assess the functional reinnervation of denervated hind limb muscles.

BACKGROUND: Spinal cord injuries induce a critical loss of motoneurons followed by irreversible locomotor function impairment. Surgical approaches combined with neuroprotective agents effectively rescue the damaged motoneurons and improve locomotor function. Our aim was to develop a reliable method which is able to provide quantifiable and in-depth data on the locomotor recovery during skeletal muscle reinnervation. NEW METHOD: Sprague-Dawley rats underwent lumbar 4 ventral root avulsion and reimplantation followed by riluzole treatment in order to rescue the injured motoneurons of the damaged pool. Control animals were operated, but received no riluzole treatment. The locomotor pattern of the hind limb was recorded biweekly on a special runway equipped with high resolution and high speed digital cameras producing both lateral and rear views simultaneously. All together 12 parameters of the hind limb movement pattern were evaluated by measuring specific joint angles, footprints and gait parameters in single video frames. Four months after the operation Fast Blue, a fluorescent retrograde tracer was applied to the L4 spinal nerve in order to label the reinnervating motoneurons. RESULTS: Our results confirmed the sensitivity of our arrangement and established strong relationship between the functional improvement and the morphological reinnervation. Moreover, we developed a correction method to make the system tolerant to the differences in the weight, step duration and step length. COMPARISON WITH EXISTING METHODS: There are no commercially available cheap, multi-parametric analysing equipment to characterise the gait in its complexity. CONCLUSIONS: Our system offers a modular, adaptable and expandable analysis on the reinnervation of the limb musculature in rodents.

Central sensitization of dorsal root potentials and dorsal root reflexes: An in vitro study in the mouse spinal cord.

BACKGROUND: Axo-axonic contacts onto central terminals of primary afferents modulate sensory inputs to the spinal cord. These contacts produce primary afferent depolarization (PAD), which serves as a mechanism for presynaptic inhibition, and also produce dorsal root reflexes (DRRs), which may regulate the excitability of peripheral terminals and second order neurons. We aimed to identify changes in these responses as a consequence of peripheral inflammation. METHODS: In vitro spinal cord recordings of spontaneous activities in dorsal and ventral roots were performed in control mice and following paw inflammation. We also used pharmacological assays to define the neurotransmitter systems implicated in such responses. RESULTS: Paw inflammation increased the frequency and amplitude of spontaneous dorsal root depolarizations, the occurrence of DRRs and the amplitude of ventral roots depolarizations. PAD was classified in two different patterns based on their relation to ventral activity: time-locked and independent events. Both patterns increased in amplitude after paw inflammation, and independent events also increased in frequency. The circuits that were responsible for this activity implicated both glutamatergic and GABAergic transmission. Adrenergic modulation differentially affected both types of PAD, and this modulation changed after paw inflammation. CONCLUSIONS: Our findings suggest the existence of independent spinal circuits at the origin of PAD and DRRs. Inflammation modulates these circuits differentially, unveiling varied mechanisms of spinal sensitization. This in vitro approach provides an isolated model for the study of the mechanisms of central sensitization and for the performance of pharmacological assays with the purpose of identifying and testing novel antinociceptive targets. SIGNIFICANCE: Spinal circuits modulate activity of primary afferents acting on central terminals. Under in vitro conditions, dorsal roots show spontaneous activity in the form of depolarizations and action potentials. Our findings are consistent with the existence of several independent generator circuits. Experimental paw inflammation reduced mechanical withdrawal threshold and significantly increased the spontaneous activity of dorsal roots, which may be secondary to an enhanced output of spinal generators. This can be considered as a novel sign of central sensitization.

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.

The Neurotrophic Effects and Mechanism of Action for FK1706 in Neurorrhaphy Rat Models and SH-SY5Y Cells.

FK1706 is a novel non-immunosuppressive immunophilin ligand with neurotrophic activity and exerts its neurotrophic effect through NGF. The present study aimed to elaborate on the neurotrophic activity and the mechanism of action of FK1706 in end-to-side neurorrhaphy rats and SH-SY5Y cells. In the regenerating nerves of neurorrhaphy rats, FK1706 increased the thickness of myelin sheath and the level of nerve regeneration-related proteins. The mechanism of action of FK1706 on neurite regrowth was elucidated in vitro by incubating SH-SY5Y cells in different conditions (Control, NGF, FK1706, NGF + FK1706, NGF + FK1706 + geldanamycin). Under the conditions where NGF was used, the phosphorylation level of major proteins (Raf-1 and ERK) in the Ras/Raf/MAPK/ERK signaling pathway related to SH-SY5Y cell proliferation was significantly enhanced following the application of FK1706. The number of viable cells, cell viability and neurite length of SH-SY5Y cells was maximal when NGF and FK1706 were used simultaneously. The binding level of HSP90 and Raf-1 in FK1706 group was the highest. These results indicated that FK1706 could significantly promote nerve regeneration after neurorrhaphy. The putative mechanism of action stated that FK1706 could promote the binding of HSP90 and Raf-1, make Raf-1 continue to be activated, thereby affecting key proteins in the Ras/Raf/MAPK/ERK signaling pathway related to the neurotrophic effects of NGF to promote the proliferation and neurite regrowth of nerve cells.

Maintenance of contractile force of the hind limb muscles by the somato-lumbar sympathetic reflexes.

This study aimed to clarify whether the reflex excitation of muscle sympathetic nerves induced by contractions of the skeletal muscles modulates their contractility. In anesthetized rats, isometric tetanic contractions of the triceps surae muscles were induced by electrical stimulation of the intact tibial nerve before and after transection of the lumbar sympathetic trunk (LST), spinal cord, or dorsal roots. The amplitude of the tetanic force (TF) was reduced by approximately 10% at 20 min after transection of the LST, spinal cord, or dorsal roots. The recorded postganglionic sympathetic nerve activity from the lumbar gray ramus revealed that both spinal and supraspinal reflexes were induced in response to the contractions. Repetitive electrical stimulation of the cut peripheral end of the LST increased the TF amplitude. Our results indicated that the spinal and supraspinal somato-sympathetic nerve reflexes induced by contractions of the skeletal muscles contribute to the maintenance of their own contractile force.

A shape-adjusted ellipse approach corrects for varied axonal dispersion angles and myelination in primate nerve roots.

Segmentation of axons in light and electron micrographs allows for quantitative high-resolution analysis of nervous tissues, but varied axonal dispersion angles result in over-estimates of fiber sizes. To overcome this technical challenge, we developed a novel shape-adjusted ellipse (SAE) determination of axonal size and myelination as an all-inclusive and non-biased tool to correct for oblique nerve fiber presentations. Our new resource was validated by light and electron microscopy against traditional methods of determining nerve fiber size and myelination in rhesus macaques as a model system. We performed detailed segmental mapping and characterized the morphological signatures of autonomic and motor fibers in primate lumbosacral ventral roots (VRs). An en bloc inter-subject variability for the preganglionic parasympathetic fibers within the L7-S2 VRs was determined. The SAE approach allows for morphological ground truth data collection and assignment of individual axons to functional phenotypes with direct implications for fiber mapping and neuromodulation studies.

Why It Is Necessary to Use the Entire Root rather than Partial Root When Doing Contralateral C7 Nerve Transfer: Cortical Plasticity Also Matters besides the Amount of Nerve Fibers.

Previous studies suggested that the mode of donor transection is a critical factor affecting the efficacy of the contralateral C7 (CC7) nerve transfer. Nevertheless, the mechanism underlying this phenomenon remains elusive. The aim of this study was to investigate the relationship between the division modes of the CC7 nerve and cortical functional reorganization of Sprague-Dawley rats. We hypothesized that different methods of CC7 nerve transection might induce differences in cortical functional reorganization, thus resulting in differences in surgery efficacy. BDNF, TNF-α/IL-6, and miR-132/134 were selected as indicators of cortical functional reorganization. No significant differences in all these indicators were noted between the entire group and the entire root+posterior division group (P > 0.05). BDNF and miR-132/134 levels in the entire group and the entire root+posterior division group were significantly increased compared with their levels in the posterior group and the blank control group (P < 0.001). In all groups, BDNF, TNF-α/IL-6, and miR-132/134 levels in both hemispheres initially increased and subsequently decreased until week 40. In conclusion, this study provided the evidence of dynamic changes in BDNF, TNF-α/IL-6, and miR-132/134 in the cortex of rats after CC7 nerve transfer using different transecting modes, demonstrating that different CC7 nerve divisions might result in different surgical effects through modulation of cortical reorganization.

Does the L5 spinal nerve move? Anatomical evaluation with implications for postoperative L5 nerve palsy.

PURPOSE: While palsy of the L5 nerve root due to stretch injury is a known complication in complex lumbosacral spine surgery, the underlying pathophysiology remains unclear. The goal of this cadaveric study was to quantify movement of the L5 nerve root during flexion/extension of the hip and lower lumbar spine. METHODS: Five fresh-frozen human cadavers were dissected on both sides to expose the lumbar vertebral bodies and the L5 nerve roots. Movement of the L5 nerve root was tested during flexion and extension of the hip and lower lumbar spine. Four steps were undertaken to characterize these movements: (1) removal of the bilateral psoas muscles, (2) removal of the lumbar vertebral bodies including the transforaminal ligaments from L3 to L5, (3) opening and removing the dura mater laterally to visualize the rootlets, and (4) removal of remaining soft tissue surrounding the L5 nerve root. Two metal bars were inserted into the sacral body at the level of S1 as fixed landmarks. The tips of these bars were connected to make a line for the ruler that was used to measure movement of the L5 nerve roots. Movement was regarded as measurable when there was an L5 nerve excursion of at least 1 mm. RESULTS: The mean age at death was 86.6 years (range 68-89 years). None of the four steps revealed any measurable movement after flexion/extension of the hip and lower lumbar spine on either side (< 1 mm). Flexion of the hip and lower lumbar spine revealed lax L5 nerve roots. Extension of the hip and lower lumbar spine showed taut ones. CONCLUSION: Significant movement or displacement of the L5 nerve root could not be quantified in this study. No mechanical cause for L5 nerve palsy could be identified so the etiology of the condition remains unclear.

Chronic neuronal activation increases dynamic microtubules to enhance functional axon regeneration after dorsal root crush injury.

After a dorsal root crush injury, centrally-projecting sensory axons fail to regenerate across the dorsal root entry zone (DREZ) to extend into the spinal cord. We find that chemogenetic activation of adult dorsal root ganglion (DRG) neurons improves axon growth on an in vitro model of the inhibitory environment after injury. Moreover, repeated bouts of daily chemogenetic activation of adult DRG neurons for 12 weeks post-crush in vivo enhances axon regeneration across a chondroitinase-digested DREZ into spinal gray matter, where the regenerating axons form functional synapses and mediate behavioral recovery in a sensorimotor task. Neuronal activation-mediated axon extension is dependent upon changes in the status of tubulin post-translational modifications indicative of highly dynamic microtubules (as opposed to stable microtubules) within the distal axon, illuminating a novel mechanism underlying stimulation-mediated axon growth. We have identified an effective combinatory strategy to promote functionally-relevant axon regeneration of adult neurons into the CNS after injury.

Biomechanical study of the C5-C8 cervical extraforaminal ligaments.

BACKGROUND: The anatomical distribution of the extraforaminal ligaments in the cervical intervertebral foramina has been well studied. However, detailed descriptions of the biomechanical characteristics of these ligaments are lacking. METHODS: The paravertebral muscles were dissected, and the extraforaminal ligaments and nerve roots were identified. The C5 and C7 or C6 and C8 cervical nerve roots on both sides were randomly selected, and a window was opened on the vertebral lamina to expose the posterior spinal nerve root segments. Five needles were placed on the nerve root and the bone structure around the intervertebral foramen; the distal end of the nerve root was then tied with silk thread, and the weights were connected across the pulley. A weight load was gradually applied to the nerve root (50 g/time, 60 times in total). At the end of the experiment, segments of the extraforaminal ligaments were selectively cut off to compare the changes in nerve root displacement. RESULTS: The displacement of the C5, C6, C7, and C8 nerve roots increases with an increasing traction load, and the rate of change of nerve root displacement in the intervertebral foramen is smaller than that in the nerve root on the outside area (p < 0.05). Extraforaminal ligaments can absorb part of the pulling load of the nerve root; the C5 nerve root has the largest load range. CONCLUSIONS: Cervical extraforaminal ligaments can disperse the tension load on the nerve root and play a role in protecting the nerve root. The protective effect of the C5 nerve root was the strongest, and this may anatomically explain why the C5 nerve roots are less prone to simple avulsion.