Axon Regeneration In Spinal Cord Research Articles

Effects of transcranial magnetic stimulation on axonal regeneration in the corticospinal tract of female rats with spinal cord injury

BackgroundThis study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI). New methodTMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored. ResultsThe TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers. Comparison with existing methodsUnlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI. ConclusionsTMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives.

The oncomodulin receptor ArmC10 enables axon regeneration in mice after nerve injury and neurite outgrowth in human iPSC-derived sensory neurons.

Oncomodulin (Ocm) is a myeloid cell-derived growth factor that enables axon regeneration in mice and rats after optic nerve injury or peripheral nerve injury, yet the mechanisms underlying its activity are unknown. Using proximity biotinylation, coimmunoprecipitation, surface plasmon resonance, and ectopic expression, we have identified armadillo-repeat protein C10 (ArmC10) as a high-affinity receptor for Ocm. ArmC10 deletion suppressed inflammation-induced axon regeneration in the injured optic nerves of mice. ArmC10 deletion also suppressed the ability of lesioned sensory neurons to regenerate peripheral axons rapidly after a second injury and to regenerate their central axons after spinal cord injury in mice (the conditioning lesion effect). Conversely, Ocm acted through ArmC10 to accelerate optic nerve and peripheral nerve regeneration and to enable spinal cord axon regeneration in these mouse nerve injury models. We showed that ArmC10 is highly expressed in human-induced pluripotent stem cell-derived sensory neurons and that exposure to Ocm altered gene expression and enhanced neurite outgrowth. ArmC10 was also expressed in human monocytes, and Ocm increased the expression of immune modulatory genes in these cells. These findings suggest that Ocm acting through its receptor ArmC10 may be a useful therapeutic target for nerve repair and immune modulation.

Defining Spatial Relationships Between Spinal Cord Axons and Blood Vessels in Hydrogel Scaffolds.

Positively charged oligo(poly(ethylene glycol) fumarate) (OPF+) hydrogel scaffolds, implanted into a complete transection spinal cord injury (SCI), facilitate a permissive regenerative environment and provide a platform for controlled observation of repair mechanisms. Axonal regeneration after SCI is critically dependent upon nutrients and oxygen from a newly formed blood supply. Our objective was to investigate fundamental characteristics of revascularization in association with the ingrowth of axons into hydrogel scaffolds, thereby defining spatial relationships between axons and the neovasculature. A novel combination of stereologic estimates and precision image analysis techniques quantitate neurovascular regeneration in rats. Multichannel hydrogel scaffolds containing Matrigel-only (MG), Schwann cells (SCs), or SCs with rapamycin-eluting poly(lactic co-glycolic acid) microspheres (RAPA) were implanted for 6 weeks following complete spinal cord transection. Image analysis of 72 scaffold channels identified a total of 2494 myelinated and 4173 unmyelinated axons at 10 μm circumferential intervals centered around 708 individual blood vessel profiles. Blood vessel number, density, volume, diameter, intervessel distances, total vessel surface and cross-sectional areas, and radial diffusion distances were compared. Axon number and density, blood vessel surface area, and vessel cross-sectional areas in the SC group exceeded that in the MG and RAPA groups. Individual axons were concentrated within a concentric radius of 200-250 μm from blood vessel walls, in Gaussian distributions, which identified a peak axonal number (Mean Peak Amplitude) corresponding to defined distances (Mean Peak Distance) from each vessel, the highest concentrations of axons were relatively excluded from a 25-30 μm zone immediately adjacent to the vessel, and from vessel distances >150 μm. Higher axonal densities correlated with smaller vessel cross-sectional areas. A statistical spatial algorithm was used to generate cumulative distribution F- and G-functions of axonal distribution in the reference channel space. Axons located around blood vessels were definitively organized as clusters and were not randomly distributed. A scoring system stratifies 5 direct measurements and 12 derivative parameters influencing regeneration outcomes. By providing methods to quantify the axonal-vessel relationships, these results may refine spinal cord tissue engineering strategies to optimize the regeneration of complete neurovascular bundles in their relevant spatial relationships after SCI. Impact statement Vascular disruption and impaired neovascularization contribute critically to the poor regenerative capacity of the spinal cord after injury. In this study, hydrogel scaffolds provide a detailed model system to investigate the regeneration of spinal cord axons as they directly associate with individual blood vessels, using novel methods to define their spatial relationships and the physiologic implications of that organization. These results refine future tissue engineering strategies for spinal cord repair to optimize the re-development of complete neurovascular bundles in their relevant spatial architectures.

Proprioception 2.0: novel functions for muscle spindles.

Muscle spindles are encapsulated mechanosensory receptors within skeletal muscle tissue that inform the central nervous system about the contractile status of each muscle. This information is required for any coordinated movement and for stable posture. This review summarizes recent findings regarding novel functions for proprioceptive feedback information, muscle spindle disease and the molecular basis of mechanoreception. Muscle spindle function is not limited to regulating motor control but is also required for appropriate realignment of fractured bones, successful regeneration of spinal cord axons after injury and spinal alignment. Several proteins responsible for or modulating mechanotransduction in proprioceptive sensory neurons have been identified, including the Piezo2 channel as a candidate for the principal mechanotransduction channel. Many neuromuscular diseases are known to be accompanied by an impaired function of muscle spindles, resulting in a decline of motor performance and coordination in the patients. Our knowledge regarding the molecular basis of muscle spindle function is still incomplete. However, increasing our understanding of mechanotransduction in muscle spindles is a prerequisite for finding appropriate strategies to prevent injuries due to unstable gait and frequent falls.

Aligned fibrous PVDF-TrFE scaffolds with Schwann cells support neurite extension and myelination in vitro

Objective. Polyvinylidene fluoride-trifluoroethylene (PVDF-TrFE), which is a piezoelectric, biocompatible polymer, holds promise as a scaffold in combination with Schwann cells (SCs) for spinal cord repair. Piezoelectric materials can generate electrical activity in response to mechanical deformation, which could potentially stimulate spinal cord axon regeneration. Our goal in this study was to investigate PVDF-TrFE scaffolds consisting of aligned fibers in supporting SC growth and SC-supported neurite extension and myelination in vitro. Approach. Aligned fibers of PVDF-TrFE were fabricated using the electrospinning technique. SCs and dorsal root ganglion (DRG) explants were co-cultured to evaluate SC-supported neurite extension and myelination on PVDF-TrFE scaffolds. Main results. PVDF-TrFE scaffolds supported SC growth and neurite extension, which was further enhanced by coating the scaffolds with Matrigel. SCs were oriented and neurites extended along the length of the aligned fibers. SCs in co-culture with DRGs on PVDF-TrFE scaffolds promoted longer neurite extension as compared to scaffolds without SCs. In addition to promoting neurite extension, SCs also formed myelin around DRG neurites on PVDF-TrFE scaffolds. Significance. This study demonstrated PVDF-TrFE scaffolds containing aligned fibers supported SC-neurite extension and myelination. The combination of SCs and PVDF-TrFE scaffolds may be a promising tissue engineering strategy for spinal cord repair.

Fluoro-Ruby as a reliable marker for regenerating fiber tracts

Axon visualization techniques are important in assessing the efficacy of interventional approaches to stimulate neural regeneration. Whereas the labeling of descending tracts in the spinal cord has been well established using the intracortical injection of biotin dextran amine (BDA), the labeling of ascending sensory fibers of the dorsal funiculus is more problematic. Fluoro-Ruby (FR; dextran tetramethylrhodamine; MW 10,000) is a bidirectional permanent tracer, but the retrograde tracing of fibers is particularly prominent, and FR is a highly sensitive tracer that can be applied in discrete injection sites. In the present report, we used FR to efficiently label ascending fibers in the dorsal columns of the rat spinal cord. After transplantation of olfactory ensheathing cells into the transected dorsal funiculus, the application of FR was able to detect regenerating ascending fibers in the spinal cord. Regenerated fibers crossing the injury site were labeled and easily identified. It is likely that the tracer was taken up by damaged fibers. As additional advantages, the labeling is resistant to photobleaching and no additional tissue processing is necessary for visualization. It can be used for in vivo as well as in vitro injections. The findings indicate that FR can be used as a reliable fluorescent marker to study ascending regenerated fibers in the spinal cord axonal regeneration.

Expression of an Activated Integrin Promotes Long-Distance Sensory Axon Regeneration in the Spinal Cord.

After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery. The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient.

Functionalized collagen scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration

Previous studies have demonstrated that several mechanisms, including numerous inhibitory molecules, weak neurotrophic stimulation and deficient intrinsic regenerative responses, collectively contribute to the failure of mature spinal cord axon regeneration. Thus, combinatorial therapies targeting multiple mechanisms have attracted much attention. In the present study, a porous collagen scaffold was used to support neuronal attachment and bridge axonal regeneration. The scaffold was specifically functionalized using neutralizing proteins (CBD-EphA4LBD, CBD-PlexinB1LBD and NEP1-40) and collagen-binding neurotrophic factors (CBD-BDNF and CBD-NT3) to simultaneously antagonize myelin inhibitory molecules (ephrinB3, Sema4D and Nogo) and exert neurotrophic protection and stimulation. Cerebellar granular neurons cultured on the functionalized collagen scaffold promoted neurite outgrowth in the presence of myelin. Furthermore, a full combinatorial treatment comprising functionalized scaffold implantation and cAMP administration was developed to evaluate the synergistic repair ability in a rat T10 complete removal spinal cord injury model. The results showed that full combinatorial therapy exhibited the greatest advantage in reducing the volume of cavitation, facilitating axonal regeneration, and promoting neuronal generation. The newborn neurons generated in the lesion area could form the neuronal relay and enhance the locomotion recovery after severe spinal cord injury. Statement of SignificanceA porous collagen scaffold was specifically functionalized with neutralizing proteins and neurotrophic factors to antagonize the myelin inhibitory molecules and exert neurotrophic protection and stimulation for spinal cord regeneration. Cerebellar granular neurons seeded on the functionalized collagen scaffold showed enhanced neurite outgrowth ability in vitro. The functionalized scaffold implantation combined with cAMP administration exhibited synergistic repair ability for rat T10 complete spinal cord transection injury.

Oscillating field stimulation promotes recovery after spinal cord injury in rats: Assessment using behavioral, electrophysiological and histological evaluations.

We explored whether oscillating field stimulation (OFS) could efficiently promote motor function recovery in rat model of spinal cord injury. SD rats with spinal cord injury induced by Allen method was divided into two groups, experimental group rats received active stimulator units and control group rats received sham (inoperative) stimulator units. The electric field intensity was 600μV/mm, and the polarity alternated every 15 min. The results showed that the experimental group rats had significantly better locomotor function recovery (inclined-plane testing and modified Tarlov motor grading scale) 5 weeks after the injury (P<;0.05). OFS treatment significantly decreased motor evoked potential (MEP) latency differences and amplitude differences 4 w and 8 w post injury (P<;0.05, P<;0.01). Furthermore, the number of axons was quantified by immunofluorescence staining of nerve fiber (NF), increased axon numbers were observed at 4 w and 8 w in experimental group (P<;0.05). These findings suggest OFS can promote motor function recovery in SCI rats, and this effect may be related to the improving axon regeneration in spinal cord.

Complement protein C1q modulates neurite outgrowth in vitro and spinal cord axon regeneration in vivo.

Traumatic injury to CNS fiber tracts is accompanied by failure of severed axons to regenerate and results in lifelong functional deficits. The inflammatory response to CNS trauma is mediated by a diverse set of cells and proteins with varied, overlapping, and opposing effects on histological and behavioral recovery. Importantly, the contribution of individual inflammatory complement proteins to spinal cord injury (SCI) pathology is not well understood. Although the presence of complement components increases after SCI in association with axons and myelin, it is unknown whether complement proteins affect axon growth or regeneration. We report a novel role for complement C1q in neurite outgrowth in vitro and axon regrowth after SCI. In culture, C1q increased neurite length on myelin. Protein and molecular assays revealed that C1q interacts directly with myelin associated glycoprotein (MAG) in myelin, resulting in reduced activation of growth inhibitory signaling in neurons. In agreement with a C1q-outgrowth-enhancing mechanism in which C1q binding to MAG reduces MAG signaling to neurons, complement C1q blocked both the growth inhibitory and repulsive turning effects of MAG in vitro. Furthermore, C1q KO mice demonstrated increased sensory axon turning within the spinal cord lesion after SCI with peripheral conditioning injury, consistent with C1q-mediated neutralization of MAG. Finally, we present data that extend the role for C1q in axon growth and guidance to include the sprouting patterns of descending corticospinal tract axons into spinal gray matter after dorsal column transection SCI.

Promotion of spinal cord axon regeneration by 3D nanofibrous core–sheath scaffolds

Since spinal cord injury is a complicated problem, neural tissue repair, and regeneration strategies have received a great deal of attention. In this study, a three-dimensional (3D) nanofibrous core-sheath scaffold with nanorough sheath and aligned core were fabricated by a combined electrospinning method with water vortex and two-nozzle system. In vitro and in vivo biological tests were carried out on the poly(lactic-co-glycolic acid) (PLGA) scaffolds. The cell morphology and proliferation evaluation of nerve cells on 3D PLGA scaffolds were studied. Cells were properly orientated along the aligned fiber direction of the scaffold. In animal studies, adult rats received a complete lateral hemisection at the T9-T10 level. Scaffolds were engrafted to bridge 3 mm defects of 10 adult rat spinal cords; 10 rats were used as controls. For 8 weeks, motor and sensory recovery by open field locomotor scale, narrow beam and tail flick tests were assessed. Locomotor and sensory scores of grafted animals were significantly better than the control group. Histological findings demonstrated that the scaffold supports the axonal regeneration of injured spinal cords and regenerating axons were seen to enter the graft and extend along its length.

Metamorphosis and the regenerative capacity of spinal cord axons in Xenopus laevis

Throughout the vertebrate subphylum, the regenerative potential of central nervous system axons is greatest in embryonic stages and declines as development progresses. For example, Xenopus laevis can functionally recover from complete transection of the spinal cord as a tadpole but is unable to do so after metamorphosing into a frog. Neurons of the reticular formation and raphe nucleus are among those that regenerate axons most reliably in tadpole and that lose this ability after metamorphosis. To identify molecular factors associated with the success and failure of spinal cord axon regeneration, we pharmacologically manipulated thyroid hormone (TH) levels using methimazole or triiodothyronine, to either keep tadpoles in a permanently larval state or induce precocious metamorphosis, respectively. Following complete spinal cord transection, serotonergic axons crossed the lesion site and tadpole swimming ability was restored when metamorphosis was inhibited, but these events failed to occur when metamorphosis was prematurely induced. Thus, the metamorphic events controlled by TH led directly to the loss of regenerative potential. Microarray analysis identified changes in hindbrain gene expression that accompanied regeneration-permissive and -inhibitory conditions, including many genes in the permissive condition that have been previously associated with axon outgrowth and neuroprotection. These data demonstrate that changes in gene expression occur within regenerating neurons in response to axotomy under regeneration-permissive conditions in which normal development has been suspended, and they identify candidate genes for future studies of how central nervous system axons can successfully regenerate in some vertebrates.

Recovery from spinal cord injury: regeneration, plasticity and rehabilitation

Experimental spinal cord injury is no longer incurable. Many papers have appeared over the past few years reporting functional recovery following a variety of treatments. These have included interventions that affect myelin inhibitory molecules and their receptors, or inhibitory chondroitin sulphate proteoglycans, and treatments in which the regenerative potential of axons has been stimulated through growth-factor receptors or manipulation of internal signalling pathways (for reviews see Buchli and Schwab, 2005; Fawcett, 2006; Hannila et al. , 2007). There has also been success with strategies that bridge the injury using various axon growth-promoting cell types (Fouad et al. , 2005; Biernaskie et al. , 2007; Raisman and Li, 2007). Functional recovery has been seen in hindlimbs and forelimbs and affecting walking, skilled movements, sensation and other outcome measures. This is all very encouraging, but it is still not entirely clear what changes are responsible for the recovery. Many of the successful treatments stimulate axon regeneration through the site of injury, but most also stimulate plasticity. In the field, plasticity is used as a term to describe short-distance sprouting above and below the lesion and changes in synaptic strength, together enabling the CNS to change its connectivity. Thus, treatments that affect NogoA signalling and chondroitin sulphate proteoglycans, in addition to stimulating spinal cord axon regeneration, also promote reactivation of ocular dominance, the most studied example of plasticity (Pizzorusso et al. , 2002; McGee et al. , 2005). Is functional return in the injured cord due to the small number of axons that regenerate, or due to plasticity in …

Physical and biological performance of a novel block copolymer nerve guide

Although the ability to regenerate is evident in the nervous system, lesioned neurites are unable to cross gaps in neuronal pathways. In order to bridge gaps, guiding cues are essential to direct neurite regrowth. To overcome many of the shortcomings of polymer-based nerve guides, we developed a bioresorbable nerve guide composed of a novel trimethylene carbonate-caprolacton block copolymer (TMC-CL). Pore formation was controlled by using special solvent/precipitation media compositions in combination with the pore forming agent poly ethylene glycol (PEG). NMR spectroscopy, shear force-, compression-, and permeation assays were used for conduit characterization. The polymer conduit has a semipermeable wall with submicron pores to allow free metabolite/drug exchange. In order to investigate the principle of temporally controlled expression of therapeutic proteins in nerve guides, Neuro-2a cells were genetically engineered to express the reporter gene product green fluorescent protein (GFP) under the control of the Tet-On system. When these transduced cells were encapsulated in nerve guides, GFP expression could be induced for days by adding the antibiotic tetracycline derivative doxycycline to the nerve guide environment. Furthermore, encapsulated dorsal root ganglia (DRG) produced long neurites in vitro. In subsequent in vivo experiments, nerve guides filled with Schwann cells (SC) were implanted into lesioned spinal cords of adult rats. Regeneration of spinal cord axons into nerve guides was promoted by co-implanted Schwann cells. The data suggest that the novel TMC-CL nerve guides provide a promising tool for neuroregeneration.

Multiple-channel scaffolds to promote spinal cord axon regeneration

As molecular, cellular, and tissue-level treatments for spinal cord injury are discovered, it is likely that combinations of such treatments will be necessary to elicit functional recovery in animal models or patients. We describe multiple-channel, biodegradable scaffolds that serve as the basis for a model to investigate simultaneously the effects on axon regeneration of scaffold architecture, transplanted cells, and locally delivered molecular agents. Poly(lactic- co-glycolic acid) (PLGA) with copolymer ratio 85:15 was used for these initial experiments. Injection molding with rapid solvent evaporation resulted in scaffolds with a plurality of distinct channels running parallel along the length of the scaffolds. The feasibility of creating scaffolds with various channel sizes and geometries was demonstrated. Walls separating open channels were found to possess void fractions as high as 89%, with accessible void fractions as high as 90% through connections 220 μm or larger. Scaffolds degraded in vitro over a period of 30 weeks, over which time-sustained delivery of a surrogate drug was observed for 12 weeks. Primary neonatal Schwann cells were distributed in the channels of the scaffold and remained viable in tissue culture for at least 48 h. Schwann-cell containing scaffolds implanted into transected adult rat spinal cords contained regenerating axons at one month post-operation. Axon regeneration was demonstrated by three-dimensional reconstruction of serial histological sections.

Why do Nogo/Nogo‐66 receptor gene knockouts result in inferior regeneration compared to treatment with neutralizing agents?

IN-1, the monoclonal antibody against the exon 3-encoded N-terminal domain of Nogo-A, and the Nogo-66 receptor (NgR) antagonist NEP1-40 have both shown efficacy in promoting regeneration in animal spinal cord injury models, the latter even when administered subcutaneously 1 week after injury. These results are supportive of the hypothesis that the Nogo-NgR axis is a major path for inhibition of spinal cord axonal regeneration and uphold the promises of these neutralizing agents in clinical applications. However, mice with targeted disruption of Nogo and NgR have, surprisingly, only modest regenerative capacity (if any) compared with treatment with IN-1 or NEP1-40. Disruption of the Nogo gene by various groups yielded results ranging from significant regenerative improvement in young mice to no improvement. Likewise, knockout of NgR produced some improvement in raphespinal and rubrospinal axonal regeneration, but not that of corticospinal neurons. Other than invoking possible differences in genetic background, we suggest here some possible and testable explanations for the above phenomena. These possibilities include effects of IN-1 and NEP1-40 on the CNS beyond neutralization of Nogo and NgR functions, and the latter's possible role in the CNS beyond that of neuronal growth inhibition.

Neuroprotection and Regeneration Strategies for Spinal Cord Repair

The journey toward a cure for spinal cord injury (SCI) has taken many paths. In this article, we review these paths, and highlight the clinical applications of these experimental repair strategies. Initial strategies involved attempts at neuroprotection with steroids and other anti-inflammatory drugs. Other anti-ischemia treatments, agents to eliminate the damage from excitotoxicity, and anti-apoptotic agents were also tried. Another avenue involved enhancing the function of the remaining uninjured axons by measures to produce remyelination and medications to improve axonal conduction. In the last two decades there has been a major effort to enhance spinal cord axonal regeneration through a variety of techniques including neutralization of neurite inhibition, administration of neurotrophic factors, implantation of synthetic channels, and transplantation of a variety of cell types. Indeed, several of these strategies have been so promising in animals that clinicians have been stimulated to explore their potential human application. We also examine the different experimental models of SCI used to assess repair, and discuss how the injury model impacts on the assessment of axonal regeneration and functional recovery after SCI. The mechanisms of recovery that may be involved after SCI will be analyzed, and their relevance toward finding a cure for human SCI. Unfortunately, the goal of producing significant functional regeneration of the human spinal cord has not yet been achieved despite the many strategies that have been developed. It is our hope that improved understanding of the mechanisms underlying functional recovery will lead to successful therapeutic strategies in humans.

A new millenium for spinal cord regeneration: growth-associated genes.

Neurons surviving spinal cord injury undergo extensive reorganization that may result in the formation of functional synaptic contacts. Many neurons, however, fail to activate the necessary mechanisms for successful regeneration. In this review, we discuss the implications of growth cone genes that we have correlated with successful spinal cord axonal regeneration. Factors that inhibit regeneration, and activation of genes that promote it are discussed. The early progress n understanding mechanisms that seem to promote or inhibit regeneration in the central nervous system may have significant clinical utility in the future.

823 Spinal Cord Axonal Regeneration Is Influenced by Embryonic Proteins

823 Spinal Cord Axonal Regeneration Is Influenced by Embryonic Proteins

823 Spinal Cord Axonal Regeneration Is Influenced by Embryonic Proteins

823 Spinal Cord Axonal Regeneration Is Influenced by Embryonic Proteins