Root Avulsion Research Articles

Multiple posttraumatic cervical pseudomeningoceles

A 4-year-old girl presented with weakness and wasting of the left upper limb following a traction injury 3 months back. Magnetic resonance imaging (MRI) of her spine (Fig. 1) demonstrated multiple, discrete, non-enhancing cystic lesions suggestive of pseudomeningoceles along the dorsal and ventral nerve root sleeves on the left side from the C3 to C7 vertebral levels. The spinal cord was displaced to the right side at some levels by the intraspinal components of these lesions (Fig. 2). There was no evidence of altered signal intensity within the cord. There was no fracture or instability of the vertebral column. There was significant atrophy of the shoulder muscles, trapezius, and the paraspinal muscles on the left side (Fig. 2A). Electromyographic evaluation demonstrated denervation from C5 to T1, with no sensory involvement. The diagnosis was consistent with that of an extensive preganglionic brachial plexus injury, with the formation of posttraumatic pseudomeningoceles caused by avulsion of multiple roots from the spinal cord. She was referred to another center for nerve transfers. Fig. 2Axial T2 MRI showing (Left) an intraspinal component of the pseudomeningocele and atrophy of the paraspinal muscles on the left side (arrow); (Right) intraspinal and foraminal components of the pseudomeningocele and cord indentation at this level. View Large Image Figure Viewer Download Hi-res image

Glenohumeral Dysplasia Following Neonatal Brachial Plexus Palsy: Presentation and Predictive Features During Infancy

To evaluate the presence and degree of glenohumeral dysplasia (GHD) in infants undergoing surgical exploration for neonatal brachial plexus palsy (NBPP) and to identify potential predictive factors of early maladaptive shoulder morphology. We included all consecutive patients with NBPP who underwent surgical exploration of their brachial plexus and who had a preoperative magnetic resonance imaging scan at our institution over a 3-year period. Demographic, therapy, and surgical data were collected. Imaging was reviewed for glenoid morphology, glenoid version, percent humeral head anterior to the scapula, and alpha angle. Of 116 infants who presented to our institution during this 3-year period, 19 (16%) underwent surgical exploration and were included in the study. Median age at the time of the scan was 16 weeks (interquartile range, 14-46 weeks). Fourteen of 19 (74%) had GHD of Waters class 2 or increased malformation. Babies who had more severe palsies underwent earlier surgery and had less severe GHD at the time of surgery than did those with less severe palsies who had surgery later. Less severe GHD was associated with more severe palsies, as indicated by Narakas classification and number of root avulsions. Active external rotation was almost universally absent whereas other shoulder movements were present to varying degrees. More severe GHD was associated with greater total shoulder active range of motion and greater pectoralis major muscle mass. Glenohumeral dysplasia occurs often and early in NBPP and may occur in the absence of restricted range of motion. Predictors include increasing age and factors related to muscular imbalance. As such, GHD likely affects the functional outcome that may be achieved with reinnervation, and early screening may improve outcomes. Prognostic IV.

Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion.

Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Here we review clinical repair strategies and current progress in experimental ventral root avulsion lesions. The current gold standard in patients with a root avulsion is nerve transfer, whereas reimplantation of the avulsed root into the spinal cord has been performed in a limited number of cases. These neurosurgical repair strategies have significant benefit for the patient but functional recovery remains incomplete. Developing new ways to improve the functional outcome of neurosurgical repair is therefore essential. In the laboratory, the molecular and cellular changes following ventral root avulsion and the efficacy of intervention strategies have been studied at the level of spinal motoneurons, the ventral spinal root and peripheral nerve, and the skeletal muscle. We present an overview of cell-based pharmacological and neurotrophic factor treatment approaches that have been applied in combination with surgical reimplantation. These interventions all demonstrate neuroprotective effects on avulsed motoneurons, often accompanied with various degrees of axonal regeneration. However, effects on survival are usually transient and robust axon regeneration over long distances has as yet not been achieved. Key future areas of research include finding ways to further extend the post-lesion survival period of motoneurons, the identification of neuron-intrinsic factors which can promote persistent and long-distance axon regeneration, and finally prolonging the pro-regenerative state of Schwann cells in the distal nerve.

Complement receptor 2 is up regulated in the spinal cord following nerve root injury and modulates the spinal cord response.

BackgroundActivation of the complement system has been implicated in both acute and chronic states of neurodegeneration. However, a detailed understanding of this complex network of interacting components is still lacking.MethodsLarge-scale global expression profiling in a rat F2(DAxPVG) intercross identified a strong cis-regulatory influence on the local expression of complement receptor 2 (Cr2) in the spinal cord after ventral root avulsion (VRA). Expression of Cr2 in the spinal cord was studied in a separate cohort of DA and PVG rats at different time-points after VRA, and also following sciatic nerve transection (SNT) in the same strains. Consequently, Cr2−/− mice and Wt controls were used to further explore the role of Cr2 in the spinal cord following SNT. The in vivo experiments were complemented by astrocyte and microglia cell cultures.ResultsExpression of Cr2 in naïve spinal cord was low but strongly up regulated at 5–7 days after both VRA and SNT. Levels of Cr2 expression, as well as astrocyte activation, was higher in PVG rats than DA rats following both VRA and SNT. Subsequent in vitro studies proposed astrocytes as the main source of Cr2 expression. A functional role for Cr2 is suggested by the finding that transgenic mice lacking Cr2 displayed increased loss of synaptic nerve terminals following nerve injury. We also detected increased levels of soluble CR2 (sCR2) in the cerebrospinal fluid of rats following VRA.ConclusionsThese results demonstrate that local expression of Cr2 in the central nervous system is part of the axotomy reaction and is suggested to modulate subsequent complement mediated effects.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0413-6) contains supplementary material, which is available to authorized users.

Diagnosis of nerve root avulsion injuries in adults with traumatic brachial plexopathies: MRI compared with CT myelography

Background: Computed tomography myelography (CTM) has been broadly adopted as the ‘gold standard’ imaging technique in the diagnosis of nerve root avulsion injuries in traumatic brachial plexopathies. CTM has the distinct advantage of better spatial resolution than magnetic resonance imaging (MRI); however, this technique is invasive and can result in significant patient discomfort. MRI, therefore, seems relatively more advantageous as it is less invasive (requires no lumbar puncture), lacks radiation exposure, has no adverse reactions related to intrathecal contrast agents and confers excellent soft-tissue contrast. Objectives: To compare the sensitivity and specificity of MRI with CTM in the diagnosis of preganglionic nerve root avulsion injuries in adults with traumatic brachial plexopathies at the Inkosi Albert Luthuli Central Hospital.Method: A retrospective comparative analysis was performed on 16 adult patients with traumatic preganglionic brachial plexopathies who underwent both MRI and CTM at Inkosi Albert Luthuli Central Hospital. Radiologists experienced in both CTM and MRI interpreted the data and a comparison was made using CTM as the gold standard. Results: The sensitivity and specificity for MRI detecting preganglionic nerve root avulsion injuries and pseudomeningoceles was 82% and 100% respectively. The interobserver agreement between CTM and MRI for the detection of preganglionic nerve root avulsion injuries was 81.25% (Kappa = 0.77) and 87.5% (Kappa = 0.84) for the detection of pseudomeningoceles. Conclusion: MRI was as sensitive as CTM at detecting preganglionic nerve root avulsion injuries and pseudomeningoceles of spinal nerve roots C7–T1 of the brachial plexus. Some mild discrepancies existed at the C5 and C6 nerve root levels. Owing to the invasiveness of the procedure and resultant patient discomfort, CTM should be reserved for complicated cases or for patients with contraindications to MRI.

Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTPσ.

Following root avulsion, spinal nerves are physically disconnected from the spinal cord. Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTPσ. Previously, a small peptide memetic of the PTPσ wedge region named ISP (Intracellular Sigma Peptide) was generated, and its capabilities to target PTPσ and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTPσ by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTPσ is a potential therapeutic strategy for root avulsion.

Medial Meniscal Root Avulsion: A Biomechanical Comparison of 4 Different Repair Constructs

To evaluate the time-zero load-to-failure strength of 4 different constructs used to repair medial meniscal root avulsions. Sixty fresh-frozen cadaveric knees with a mean age of 74 years were used for this study. Each knee was dissected to isolate the attachment of the posterior root of the medial meniscus to the tibial plateau. An Instron machine (Instron, Norwood, MA) with a custom-designed clamp was used to avulse the intact posterior meniscal root in 12 control specimens. An additional 48 specimens were tested after transection of the native meniscal root to evaluate the pullout strength of 4 different repair constructs using No. 0 FiberWire suture (Arthrex, Naples, FL): a single suture (n= 12), a double suture (n= 12), a loop stitch (n= 12), and a locking loop stitch (n= 12). Analysis of variance was used to compare load to failure and stiffness of all 4 groups; pair-wise, between-group differences were also assessed. Repair failure occurred most commonly by suture pullout in 94% of the specimens in the repair groups. For the controls, failure occurred most commonly at the meniscus-clamp interface. Failure load was highest for the control group (mean, 359.5 ± 168 N), followed in descending order by the locking loop stitch (191.4 ± 45.1 N), loop stitch (119.6 ± 55.0 N), double suture (96.2 ± 51.4 N), and single suture (58.2 ± 29.6 N). The control group was significantly stronger than 3 of the experimental groups (single suture [95% CI, 3.8 to 11.3], double suture [95% CI, 2.1 to 6.4], and loop stitch [95% CI, 2.0 to 4.5]; P < .0001) but not the locking loop stitch (P= .003; 95% CI, 1.2 to 3.2). The locking loop stitch was significantly stronger than the single suture (P< .0001; 95% CI, 2.0 to 5.4) and double suture (P= .003; 95% CI, 1.2 to 2.9). The locking loop stitch was significantly stiffer than the single suture (P < .0001; 95% CI, 3.8 to 20.3), double suture (P < .0001; 95% CI, 2.0 to 9.8), and loop stitch (P= .03; 95% CI, 1.1 to 5.5) but not significantly different from the control group (P= .93; 95% CI, 0.3 to 1.9). Age and gender had no effect on pullout strength. The results of this study show that the locking loop stitch provided time-zero load-to-failure strength that most closely approximated the strength of the native meniscal root in addition to being significantly stronger and stiffer than 3 other commonly used repair methods. The true strength of the native meniscal root is unknown based on limitations with our testing methodology. The locking loop stitch exhibited the highest load to failure and stiffness of the 4 fixation methods tested, despite the fact that none of the fixation methods replicated the strength of the intact meniscal root. It is currently unknown what strength of fixation is required for healing of meniscal root repairs.

Preserved cutaneous silent period in cervical root avulsion

Objective: Brachial plexus injuries are usually severe and involve the entire brachial plexus, sometimes occurring with root avulsions. Imaging and electrodiagnostic studies are an essential part of the lesion evaluation; however, the results sometimes show a discrepancy. The cutaneous silent period (SP) is a spinal inhibitory reflex mediated by small-diameter A-delta nociceptive fibers. The aim of the study was to determine if cutaneous SP testing may serve as a useful aid in evaluation of brachial plexus injury and/or in the diagnosis of root avulsion.Methods: In 19 patients with traumatic brachial plexus injury (15 males, age 18–62 years) we performed a clinical examination, CT myelography and neurophysiological testing. A needle EMG was obtained from muscles supplied by C5-T1 myotomes. Cutaneous SP was recorded after painful stimuli were delivered to the thumb (C6 dermatome), middle (C7) and little (C8) fingers while subjects maintained voluntary contraction of intrinsic hand muscles.Results: Electrodiagnostic and imaging studies confirmed root avulsion (partial or total) maximally involving C5, C6 roots in 12 patients, whereas only in 4 of them the cutaneous SP was partially absent. In the remaining subjects, the cutaneous SP was preserved.Conclusion: In brachial plexopathy even with plurisegmental root avulsion, the cutaneous SP was mostly preserved. This method cannot be recommended as a reliable test for diagnosis of single root avulsion; however, it can provide a quick physiological confirmation of functional afferent A-delta fibers through damaged roots and/or trunks. The clinicians may add this test to the diagnosis of spinal cord dysfunction.

Influence of contralateral homologous cortices on motor cortical reorganization after brachial plexus injuries in rats

Brachial plexus injuries induce corresponding cortical representations to be occupied by adjacent cortices. The purpose of this study was to clarify if contralateral homologous motor regions of adjacent cortices influence occupation of deafferented motor cortex. 36 rats were divided into 3 groups of 12 each. In group 1, total brachial plexus root avulsion (tBPRA) was made on the left side. In group 2, rats underwent left tBPRA combined with corpus callosum transection (CCX). In group 3, only CCX was performed. 6 rats in each group were used for intracortical microstimulation (ICMS) to map representations of motor cortex in the right hemisphere at 7 days and the other 6 rats, at 3 months. 18 more rats without any operation underwent ICMS, with 6 each taken to serve as normal control for motor cortical representations' changes caused by different surgery. Results showed that in groups 1 and 2, sites for motor cortical representations of vibrissae, of neck and of the hindlimb was statistically more than that of control, respectively, and statistically more sites were found at 3 months than at 7 days, respectively. At the two time points, sites for vibrissa cortices and that for the hindlimb were statistically more in group 2 than in group 1, respectively. CCX alone did not induce change of site number for motor cortical representations. We conclude that after tBPRA, contralateral homologous motor cortices may, to some extent, prevent neighboring cortices from encroachment on motor cortical representations of the brachial plexus.

The neuroprotective effect of erythropoietin on spinal motor neurons after nerve root avulsion injury in rats.

The rapid death of many spinal motor neurons after nerve root avulsion injury results in limited functional recovery following replantation surgery of avulsed nerves into the spinal cord. Therefore, we investigated the neuroprotective effect of erythropoietin (EPO) on motor neurons after nerve root avulsion injury using a rat model. After C6 nerve root avulsion injury, EPO (2680 U/kg) was injected subcutaneously once a day for 3 consecutive days with various starting time points. At 28 and 56 days after injury, histological and immunohistological investigations were performed. EPO-treated rats showed a significant increase in the number of surviving motor neurons at day 28 when the initial dose was started within 96 h after injury. In EPO-treated rats, superoxide formation in the motor neurons and proliferation of microglia were markedly suppressed in the acute phase. GAP-43-positive surviving motor neurons were significantly increased in EPO-treated rats at day 28. However, at 56 days after surgery, EPO-treated rats showed a much greater decrease of surviving motor neurons compared with those at day 28. The neuroprotective effect of EPO is not long lasting, but may prolong the time before replantation surgery.

Influence of lateral meniscal posterior root avulsions and the meniscofemoral ligaments on tibiofemoral contact mechanics.

The purpose of this study was to investigate the effect of lateral meniscal posterior root avulsions combined with intact meniscofemoral ligaments (MFLs), deficient MFLs, anterior cruciate ligament (ACL) tears and reconstructions, and root repairs using an established tibiofemoral contact mechanics testing protocol. Ten fresh-frozen cadaveric knees were tested with six knee conditions (1: intact; 2: lateral meniscal posterior root avulsion; 3: root avulsion and deficient MFLs; 4: condition3 with ACL tear; 5: condition4 with ACL reconstruction; 6: ACL reconstruction with root repair) at five flexion angles (0°, 30°, 45°, 60°, and 90°), under a 1000-N axial load. Contact area and pressure were measured with Tekscan sensors. Compared to the intact state, condition2 did not significantly change lateral compartment contact area or pressure. Changes in contact mechanics were greater at increased flexion angles; for condition3 at 0° and 90°, contact area decreased 37 and 52% [95% CI (21-53) and (39-66), respectively] and mean contact pressure increased 55 and 87% [95% CI (33-76) and (59-114), respectively]. Root repair with ACL reconstruction was not significantly different from the intact state. The MFLs protect the lateral compartment from changes in contact mechanics in the setting of a lateral meniscal posterior root avulsion, whereas a combination of lateral meniscal root avulsion and deficient MFLs leads to significant changes. Concurrent ACL reconstruction and lateral meniscal root repair restore mean contact pressure and area to the intact state and are recommended in this combined injury to prevent or slow the development of lateral compartment arthritis.

Neuroprotection and reduction of astroglial reaction by human embryonic stem cell engrafting following spinal cord ventral root avulsion

Neuroprotection and reduction of astroglial reaction by human embryonic stem cell engrafting following spinal cord ventral root avulsion

Remote Paraparesis due to a Traumatic Extradural Arachnoid Cyst Developing 2 Years after Brachial Plexus Root Avulsion Injury: Case Report and Review of the Literature

Traumatic extradural arachnoid cyst is a rare entity. However, late appearance of paraparesis due to formation of an extradural arachnoid cyst as a sequel of brachial plexus injury is extremely rare and the literature regarding this issue is scarce revealing only 11 cases. Herein, we report a patient with delayed progressive spastic paraparesis appearing after a multilevel brachial plexus root avulsion injury where imaging revealed formation of a large traumatic extradural arachnoid cyst at the cervicothoracic region. Furthermore, to propose that a high-energy trauma might simultaneously result in delayed formation of an extradural arachnoid cyst. However, preganglionic root avulsion injury with pseudomeningocele formation in association with extradural arachnoid cyst is not reported previously. A case of a 36-year-old man with spastic paraparesis developing 2 years after a multilevel brachial plexus root avulsion injury is presented. Root avulsion had immediately resulted in complete paralysis of the left upper limb that had not ameliorated. Imaging studies of the cervicothoracic region disclosed left-sided multilevel pseudomeningoceles and a large extradural arachnoid cyst extending from C5 to T2. After appropriate en bloc laminotomy, the cyst was excised and the causative dural tear was closed. Subsequently, three large defects of pseudomeningoceles were obliterated with artificial dural patch for the prevention of cord herniation. This was followed with laminoplasty of the corresponding levels after dural closure. The postoperative course was uneventful and paraparesis recovered steadily within 2 months. Paraparesis even years after brachial plexus injury should be regarded as a serious event that deserves extensive imaging survey for the possibility of the formation of an extradural arachnoid cyst. Careful review of the literature disclosed that the current case is the 12th case that an extradural arachnoid cyst has developed after brachial plexus injury and the first example that the pathogenic factor that might be implicated in occurrence of this rare association could be clarified with review of the MRI features. Actually, the presence of posttraumatic pseudomeningoceles in association with an arachnoid cyst in the current case is in favor of the belief that only preganglionic root injuries that are in close proximity to the spinal canal had been the cause dural tear with remote formation of extradural arachnoid cyst.

Isolated C5–C6 avulsion in obstetric brachial plexus palsy treated by ipsilateral C7 neurotization to the upper trunk: outcomes at a mean follow-up of 9 years

Cervical root avulsions are the worst pattern of injury in obstetrical brachial plexus injury (OBPI). The prognosis is poor and the treatment is mainly surgical with extraplexual neurotizations or muscle transfers. We present the outcomes of a technique performed in our institution to treat C5-C6 avulsion in obstetrical brachial plexus injury. This technique consists of a total ipsilateral C7 neurotization to the upper trunk. Ten babies with isolated C5-C6 root avulsion were operated on; we were able to review nine of them at over 12 months follow-up. The shoulder and the elbow function were assessed, as well as the Mallet Score. The mean follow-up was 9.2 years (SD 5.7). After a follow-up of 6 years, elbow flexion was restored with a range of motion ⩾130° and a motor function ⩾M3 in all patients. The average Mallet score was 18.1 (SD 1.2). This approach appears to be a viable alternative to extraplexual neurotizations for the treatment of C5-C6 nerve root avulsion.

Neuroplasticity and Brachial Plexus Injury

Traumatic damage to the brachial plexus is associated with temporary or permanent motor and sensory dysfunction of the upper extremity. It may lead to the severe disability of the patient, often excluded from the daily life activity. The pathomechanism of brachial plexus injury usually results from damage detected in structures taking origin in the rupture, stretching or cervical roots avulsion from the spinal cord. Often the complexity of traumatic brachial plexus injury requires a multidisciplinary diagnostic process including clinical evaluation supplemented with clinical neurophysiology methods assessing the functional state of its structures. Their presentation is the primary goal of this paper.The basis for the diagnosis of brachial plexus function is a clinical examination and neurophysiology studies: electroneurography (ENG), needle electromyography (EMG), somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) assessing the function of individual brachial plexus elements.The ENG and EMG studies clarify the level of brachial plexus damage, its type and severity, mainly using the Seddon clinical classification. In contrast to F-wave studies, the use of the MEPs in the evaluation of traumatic brachial plexus injury provides valuable information about the function of its proximal part. MEPs study may be an additional diagnostic in confirming the location and extent of the lesion, considering the pathomechanism of the damage. Clinical neurophysiology studies are the basis for determining the appropriate therapeutic program, including choice of conservative or reconstructive surgery which results are verified in prospective studies.

Biomechanical Consequences of Lateral Meniscal Posterior Root Avulsions

Objectives:Lateral meniscal posterior root avulsions are commonly found with anterior cruciate ligament (ACL) tears. The purpose of this study was to investigate the biomechanical effects of lateral meniscal posterior root avulsions with and without intact meniscofemoral ligaments (MFLs), and with concurrent ACL tears, on lateral compartment contact mechanics.Methods:A controlled laboratory study was performed using ten nonpaired fresh-frozen cadaveric knees. Tekscan sensors were used to simultaneously measure contact area and pressure (Figure) in the lateral and medial compartments. Specimens were tested with 6 conditions (1: Intact; 2: Lateral meniscal posterior root avulsion; 3: Root avulsion and torn MFL; 4: Condition 3 with ACL tear; 5: Condition 4 with ACL reconstruction; 6: ACL reconstruction with root repair) at 5 flexion angles (0, 30, 45, 60, and 90 degrees), under a 1000 N axial load.Results:Compared to the intact state, condition 2 did not significantly alter lateral compartment contact area or pressure (p < 0.05). A significant decrease in contact area and increase in mean contact pressure occurred in condition 3. Conditions 4 and 5 (ACL tear and reconstruction of the ACL, respectively, both with deficient MFLs and lateral meniscal posterior root avulsion) also produced significantly lower contact areas than the intact condition (p < 0.05), and were not substantially different than Condition 3 (Figure). Changes in contact mechanics tended to be greater at increased flexion angles; for condition 3 at 0 and 90 degrees, contact area decreased 37% and 52% (95% CI [21,53] and [39,66], respectively) and mean contact pressure increased 55% and 87% (95% CI [33,76] and [59,114], respectively). Condition 6 (root repair with ACL reconstruction) was not significantly different from the intact state (p < 0.05).Conclusion:The meniscofemoral ligaments protect the lateral compartment from changes in contact mechanics in the setting of a lateral meniscal posterior root avulsion, whereas combined lateral meniscal root avulsion and deficient meniscofemoral ligaments leads to substantial changes. Concurrent ACL reconstruction and root repair restores contact area and mean contact pressure to the intact state.

Development of a novel experimental rat model for brachial plexus avulsion injury.

Brachial plexus injuries (BPI) are devastating events that frequently result in severe functional impairment of the upper extremity, and yet, present surgical reconstruction provides limited results. An animal model is an important tool to study peripheral nerve repair and regeneration. Here, a passive traction apparatus that allowed a multidirectional force exerted on a fixed forelimb was designed to produce a BPI rat model in a noninvasive manner. Behavioral and histological analyses were carried out to assess the suitability of the model. Using the apparatus, a reproducible upper BPI model was established with the forelimb abducted 30° and a test weight of 2 kg. Avulsion of the nerve roots resulted in almost a total loss of forelimb function and the average Terzis score was decreased significantly compared with the sham group. No obvious recovery of shoulder and elbow movements was noted during the test period. In addition, nerve roots avulsion injury led to severe retrograde degeneration of motoneurons in the C5-C7 spinal cord segments. Nissl staining results showed that motoneurons decreased significantly in number and appeared to have irregular morphologies. These results indicated that a novel noninvasive rat model for BPI that simulates the mechanism of a human lesion could be produced using our passive traction apparatus, and it is expected to produce reliable preclinical evidence in the assessment of new therapeutic strategies for this lesion.

Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury.

Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.

Identification of the Avulsion-Injured Spinal Motoneurons.

In laboratory studies, counting the spinal motoneurons that survived axonal injury is a major method to estimate the severity and regenerative capacity of the injured motoneurons after the axonal injury and rehabilitation surgery. However, the typical motoneuron marker, the choline acetyltransferase (ChAT), could not be detected in the injured motoneurons within the first 3–4 weeks postinjury. It is necessary to explore the useful and reliable specific phenotypic markers to assess the fate of injured motoneurons in axonal injury. Here, we used the fluorogold to retrograde trace the injured motoneurons in the spinal cord and studied the expression patterns of the alpha-motoneuron marker, the neuronal nuclei DNA-binding protein (NeuN) and the peripheral nerve injury marker, the activating transcriptional factor (ATF-3), and the oxidative stress marker, the neuronal nitric oxide synthase (nNOS) within the first 4 weeks of the root avulsion of the right brachial plexus (BPRA) in the adult male Sprague-Dawley rats. Our results showed that ATF-3 was rapidly induced and sustained to express only in the nuclei of the fluorogold-labeled injured motoneurons but none in the unaffected motoneurons from the 24 h of the injury; meanwhile, the NeuN almost disappeared in the avulsion-affected motoneurons within the first 4 weeks. The nNOS was not detected in the motoneurons until the second week of the injury. On the basis of the present data, we suggest that ATF-3 labels avulsion-injured motoneurons while NeuN and nNOS are poor markers within the first 4 weeks of BPRA.

Evaluation of Avulsion-Induced Neuropathology in Rat Spinal Cords with 18F-FDG Micro-PET/CT.

Brachial plexus root avulsion (BPRA) leads to dramatic motoneuron death and glial reactions in the corresponding spinal segments at the late stage of injury. To protect spinal motoneurons, assessment of the affected spinal segments should be done at an earlier stage of the injury. In this study, we employed 18F-FDG small-animal PET/CT to assess the severity of BPRA-induced cervical spinal cord injuries. Adult Sprague-Dawley rats were randomly treated and divided into three groups: Av+NS (brachial plexus root avulsion (Av) treated with normal saline), Av+GM1 (treated with monosialoganglioside), and control. At time points of 3 day (d), 1 week (w), 2 w, 4 w and 8 w post-injury, 18F-FDG micro-PET/CT scans and neuropathology assessments of the injured spinal roots, as well as the spinal cord, were performed. The outcomes of the different treatments were compared. The results showed that BPRA induced local bleeding and typical Wallerian degeneration of the avulsed roots accompanied by 18F-FDG accumulations at the ipsilateral cervical intervertebral foramen. BPRA-induced astrocyte reactions and overexpression of neuronal nitric oxide synthase in the motoneurons correlated with higher 18F-FDG uptake in the ipsilateral cervical spinal cord during the first 2 w post-injury. The GM1 treatment reduced BPRA-induced astrocyte reactions and inhibited the de novo nNOS expressions in spinal motoneurons. The GM1 treatment also protected spinal motoneurons from avulsion within the first 4 w post-injury. The data from this study suggest that 18F-FDG PET/CT could be used to assess the severity of BPRA-induced primary and secondary injuries in the spinal cord. Furthermore, GM1 is an effective drug for reducing primary and secondary spinal cord injuries following BPRA.