However, this regeneration was observed only when the grafts were caudalized NSPCs or primary spinal cord–derived NSPCs, demonstrating that the characteristics of the graft were a vital ingredient for CST regeneration (Kadoya et al., 2016). 40, 3120–3127. One of these inhibitory molecules is called Rho (Greek, rhō). J. Neurosci. Curr. Safety of Autologous human Schwann cell transplantation in subacute thoracic spinal cord injury. "We have demonstrated that stem cell therapy is safe in people with ALS. Pathological changes of distal motor neurons after complete spinal cord injury. Mater. When considering the capability of DTI to delineate neural tracts, several limitations of the method need to be understood. After ChABC was administered by intrathecal injection of a methylcellulose hydrogel containing ChABC, human-derived directly reprogrammed oligodendrocyte progenitor cells (drOPCs) were transplanted into the injured spinal cord of rats. The immature synaptic contacts, both presynaptic and postsynaptic components, undergo a process of stabilization in order to generate and maintain expression levels of neurotransmitters and their receptors to become functional (Kneussel et al., 1999; Easley-Neal et al., 2013). One of the mechanisms through which functional improvements occur in subjects with SCI is through neural plasticity, or the ability of the CNS to reorganize its circuits over time (Adler et al., 2017; Wang et al., 2018a). Although promising, cell transplantation is o en overturned by the poor cell survival in the treatment of spinal cord injuries. Stem cell transplantation as a strategy for spinal cord regeneration is at the forefront now. (2017). doi: 10.1016/j.jconrel.2017.06.030, Satkunendrarajah, K., Karadimas, S. K., Laliberte, A. M., Montandon, G., and Fehlings, M. G. (2018). |, Wallerian Degeneration and Axonal Dieback, Definition of Regeneration in the Injured Spinal Cord, Confirming Changes in Spinal Cord Connectivity, Key Factors Affecting Regenerative Failure of Spinal Cord Connectivity, Therapeutic Approaches to Overcome Obstacles in the Lesion Core and Promote Regeneration, How Engrafted Stem Cells Contribute to Spinal Cord Connectivity, Combinatorial Therapies Including Neural Stem/Progenitor Cell Transplantation and Biomaterial Scaffolds, Creative Commons Attribution License (CC BY). 33, 5655–5667. Splenic involvement in umbilical cord matrix-derived mesenchymal stromal cell-mediated effects following traumatic spinal cord injury. The treatment strategies for SCI have been shifting toward a combinatorial approach, and with the many beneficial characteristics provided by biomaterial scaffolds (Pawar et al., 2015; Chedly et al., 2017; Ropper et al., 2017; Santhosh et al., 2017; Ghosh et al., 2018; Oudega et al., 2018), it is not surprising that many studies have incorporated scaffolds into their treatment paradigms. doi: 10.1371/journal.pone.0037589, Karus, M., Ulc, A., Ehrlich, M., Czopka, T., Hennen, E., Fischer, J., et al. Figure 1. 38, 5399–5414. Chondroitinase gene therapy improves upper limb function following cervical contusion injury. Fibrotic scarring was originally reported to originate from meningeal cells following CNS injury, but recent research has shifted the focus to PDGFRβ-positive pericytes and CD13-positive endothelial cells as an active source of the cellular composition of the fibrotic scar in SCI (Soderblom et al., 2013). J. Neurosurg. Brain Res. Glia 63, 1101–1125. Long-distance retraction of injured axons coincides with the infiltration of monocytes/macrophages, whose phenotypes transition from anti-inflammatory to pro-inflammatory in response to myelin debris (Wang et al., 2015). Previously identified common post-injury adverse events in traumatic spinal cord injury-validation of existing literature and relation to selected potentially modifiable comorbidities: a prospective canadian cohort study. (2009). doi: 10.1016/j.clineuro.2012.01.003, Stroman, P. W., Khan, H. S., Bosma, R. L., Cotoi, A. I., Leung, R., Cadotte, D. W., et al. J. Magn. Spine 39, 213–219. View all Med. 14, 69–74. Chem. 16, 7900–7916. Spinal cord injuries can result in severe neurological dysfunction, including motor, sensory, and autonomic paralysis, and up until now there has been no cure or effective treatment for such injuries. 38, 745–753. Neurosurg. Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury. doi: 10.1038/416636a, Breckwoldt, M. O., Pfister, F. M., Bradley, P. M., Marinkovic, P., Williams, P. R., Brill, M. S., et al. doi: 10.1523/jneurosci.1709-08.2008, Hill, C. E., Moon, L. D., Wood, P. M., and Bunge, M. B. Microvascular endothelial cells engulf myelin debris and promote macrophage recruitment and fibrosis after neural injury. Stem Cells and Regeneration of the Spinal Cord: Practical Barriers and New Cell Technologies . doi: 10.1523/jneurosci.1151-09.2009, Bush, T. G., Puvanachandra, N., Horner, C. H., Polito, A., Ostenfeld, T., Svendsen, C. N., et al. doi: 10.15252/embj.201490578, James, N. D., Shea, J., Muir, E. M., Verhaagen, J., Schneider, B. L., and Bradbury, E. J. doi: 10.7554/eLife.39016, Wang, Y., Xie, H., and Zhao, X. (2015). doi: 10.1089/neu.2010.1741, Chu, G. K., Yu, W., and Fehlings, M. G. (2007). Required growth facilitators propel axon regeneration across complete spinal cord injury. Figure altered with permission from Nori et al. Hybrid crosslinked methylcellulose hydrogel: a predictable and tunable platform for local drug delivery. Med. Cell 165, 207–219. (2009). 114, 460–470. U.S.A. 114, E820–E829. Stem Cell Reports 5, 264–277. 8, 260–270. Neuroscience 148, 668–682. 509, 382–399. doi: 10.1093/brain/awt259, Kuroiwa, M., Watanabe, M., Katoh, H., Suyama, K., Matsuyama, D., Imai, T., et al. A., Filbin, M. T., et al. Glia 63, 635–651. J. Neurosci. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. J. Mol. Nat. The site of interactive communication between a transmitting cell (a presynaptic upper motor neuron) and a receiving one (a postsynaptic lower motor neuron) is called the synapse. 189, 204–221. Unfortunately, the problem is multi … (2014). While neural tracers have been available for some time, the technique has been utilized in only a small fraction of researchers examining SCI due to the difficulty in analyzing and interpreting the results. Dis. U.S.A. 112, 13354–13359. Cell Death Differ. Cell Res. Biomaterial scaffolds, which provide a growth-permissive substrate for axons to grow, are a logical option to accompany stem cells and will be described later. J. Neurosci. Direct injection of manganese ions into the lumbar spinal cord demonstrated enhancement of a wide rostral-caudal area of the thoracic gray matter, demonstrating its possible use to visualize the connectivity of the spinal cord (Stieltjes et al., 2006). Necroptosis, a novel type of programmed cell death, contributes to early neural cells damage after spinal cord injury in adult mice. (2013). This grouping of macrophages into M1 and M2 groups may be an oversimplification with macrophages actually being somewhere on this spectrum of polarization, but this bimodal characteristic of infiltrating macrophages has improved our understanding of their function in the injured spinal cord (Kroner et al., 2014; Wang et al., 2015). Neuron 100, 120–134.e6. Longitudinal MEPs, but not SEPs, have been shown to correlate with neurological impairment after SCI (Huang et al., 2018), but their changes may not necessarily be linked with actual phenotypical functional recovery. doi: 10.1016/j.conb.2014.03.010, Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, D., et al. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats. HK and KY reviewed the literature, wrote and edited the manuscript, and finalized and approved the manuscript. Stem Cells Transl. Meaning of self-management from the perspective of individuals with traumatic spinal cord injury, their caregivers, and acute care and rehabilitation managers: an opportunity for improved care delivery. Neurol. J. Neurosci. Previous reports showed that a combinatorial treatment strategy using stem cells and ChABC promoted functional recovery in the chronic phase of SCI (Karimi-Abdolrezaee et al., 2010; Suzuki et al., 2017; Nori et al., 2018), demonstrating that ChABC treatment can modify the chronically injured spinal cord into a microenvironment conducive to regenerative cell-based therapy. While the plasticity of neural circuits in the injured spinal cord has long been proposed to be one of the mechanisms leading to functional recovery from SCI, many studies have only presented fragmentary circumstantial evidence of plasticity. Manganese ions are calcium analogs that can enter neurons through voltage-gated calcium channels, be transported along axons by microtubule-dependent axonal transport, and cross synapses to neighboring neurons (Bedenk et al., 2018). (2014). 23, 733–741. (2018). The lower motor neurons take the impulse to the effector (muscle fibers) and control the coordination of muscle contraction. Cell 164, P526–P537. (2018). doi: 10.1016/j.cell.2014.07.017, Yang, C. Y., Song, B., Ao, Y., Nowak, A. P., Abelowitz, R. B., Korsak, R. A., et al. Med. 7, 269–277. Neuroscience 103, 203–218. doi: 10.1152/jn.00899.2005, Soderblom, C., Luo, X., Blumenthal, E., Bray, E., Lyapichev, K., Ramos, J., et al. Because whilst the research is still in its infancy, legitimate trials are showing promising results. Many of the pathways involved in cell death after SCI have been studied as possible targets of therapeutic intervention, but the results have been mixed. (2017). doi: 10.1523/jneurosci.2488-08.2008, Hou, S., Duale, H., Cameron, A. Human oligodendrogenic neural progenitor cells delivered with chondroitinase ABC facilitate functional repair of chronic spinal cord injury. 101, 1552–1566. Neurosci. UT Southwestern Medical Center researchers successfully boosted the regeneration of mature nerve cells in the spinal cords of adult mammals -- … The normally quiescent ependymal cells self-renew in response to SCI and differentiate into oligodendrocytes and astrocytes (Ke et al., 2006; Barnabe-Heider et al., 2010). doi: 10.1089/neu.2016.4498, von Leden, R. E., Khayrullina, G., Moritz, K. E., and Byrnes, K. R. (2017). doi: 10.1089/neu.2017.5434, Fehlings, M. G., Martin, A. R., Tetreault, L. A., Aarabi, B., Anderson, P., Arnold, P. M., et al. Complete – A complete spinal cord injury is where the spinal cord is completely severed, thus eliminating the chances for any nerve signals to be transmitted below the site of the injury. Therefore, in the interest of clarity, we have elected to unify the designation of these cells as NSPCs. Role of ERK1/2 MAPK signaling in the maintenance of myelin and axonal integrity in the adult CNS. Transplanted SCs have been shown to remyelinate axons and improve neural conduction similar to OPCs, and are reported to produce growth factors, extracellular components, and adhesion molecules that promote functional recovery after SCI (Golden et al., 2007; Papastefanaki et al., 2007; Cao et al., 2010; Lavdas et al., 2010; Deng et al., 2013). doi: 10.1523/jneurosci.3214-17.2018, Tran, A. P., Warren, P. M., and Silver, J. doi: 10.1038/nature17623, Anderson, M. A., O’Shea, T. M., Burda, J. E., Ao, Y., Barlatey, S. L., Bernstein, A. M., et al. 29, 9967–9976. If stem cell transplants could be engineered to further stimulate the proliferation of ependymal cells, the synergistic effect between the transplanted exogenous stem cells and endogenous stem cells may bring about greater recovery compared to either stem cell population alone. (2011). doi: 10.1016/j.expneurol.2011.09.008, Ankeny, D. P., Guan, Z., and Popovich, P. G. (2009). After inducing a severe crush SCI, biomaterial depots delivering fibroblast growth factor 2 (FGF2) and epidermal growth factor (EGF), in combination with and without glial-derived neurotrophic factor (GDNF) or an integrin-function-blocking antibody, were injected into the spinal cord. The low thermal stability and the short half-life of ChABC make it necessary to repeatedly or continually administer the drug through invasive channels (Lee et al., 2010), and its bacterial origin raises concerns about its safety and immunogenicity (Prabhakar et al., 2009). J. Med. eLife 7:e39016. The F-wave is the second voltage change observed after the M-wave, and is the muscle response to the backfire of motor neurons that were stimulated by the antidromic (proximally transmitted) impulses. Neural stem cells (NSCs) have gained increasing attention as promising regenerative therapy of SCI. Spinal Cord Regeneration Stem Cells Show Promise Over the past several years, we have shared a number of articles on the topic of stem cells in spinal cord injury research. Neurobiol. The spinal cord is responsible for relaying signals up and down the body from the brain to the nervous system. J. Clin. 11), 3362–3377. doi: 10.1016/j.cell.2015.12.037, Rosenzweig, E. S., Brock, J. H., Lu, P., Kumamaru, H., Salegio, E. A., Kadoya, K., et al. Neuron 83, 1098–1116. . doi: 10.1002/glia.23533, Easley-Neal, C., Fierro, J. Jr., Buchanan, J., and Washbourne, P. (2013). Neuroscience 265, 302–312. Neural stem cells transplanted into the lumbar ventral horn migrated to the central canal and have been shown to stimulate proliferation of ependymal cells and their differentiation into neural precursors and neurons (Xu et al., 2012). Brain 133(Pt. doi: 10.1089/neu.2009.0934, Stieltjes, B., Klussmann, S., Bock, M., Umathum, R., Mangalathu, J., Letellier, E., et al. (2016). Alternatively, the … A novel growth-promoting pathway formed by GDNF-overexpressing Schwann cells promotes propriospinal axonal regeneration, synapse formation, and partial recovery of function after spinal cord injury. (2013). J. Neurosci. Animal studies up until a decade ago had often demonstrated a significant functional improvement with various interventions, citing significantly lower inflammation, smaller cavity size, higher axonal growth, or increased myelination as possible explanations for the observed recovery, but the true reason for the improvement was often left within a black box (Badhiwala et al., 2018). It involves failure of membrane integrity, mitochondrial damage, rapid loss of ATP, sudden loss of ionic homeostasis, and induction of ROS that leads to organelle as well as cell swelling and terminates with the disposal of cell corpses in the absence of obvious phagocytic and lysosomal involvement. p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury. Nature 497, 332–337. As we have outlined in this review, significant progress has been made in the recent decades to elucidate the pathophysiology of SCI and to uncover the mechanisms that make the injured spinal cord refractory to regeneration. Tech. doi: 10.1016/j.expneurol.2005.08.020, Casha, S., Zygun, D., McGowan, M. D., Bains, I., Yong, V. W., and Hurlbert, R. J. doi: 10.1073/pnas.1616340114, Roseberry, T. K., Lee, A. M., Lalive, A. L., Wilbrecht, L., Bonci, A., and Kreitzer, A. C. (2016). In fact, ChABC in combination with neural stem/progenitor cells (NSPCs) was shown to promote functional recovery even in the chronic phase of SCI (Karimi-Abdolrezaee et al., 2010; Suzuki et al., 2017). Arrowheads indicate postsynaptic density. doi: 10.1038/nm1331, Bareyre, F. M., Kerschensteiner, M., Raineteau, O., Mettenleiter, T. C., Weinmann, O., and Schwab, M. E. (2004). Bull. Adeno-associated viral vectors (AAV) were injected 2 weeks before injury to reactivate intrinsic propriospinal neuronal growth capacity through phosphatase and tensin homologue (PTEN) knockdown or by expressing osteopontin, insulin-like growth factor 1 (IGF1) and ciliary-derived neurotrophic factor (CNTF). doi: 10.1016/j.cell.2018.02.004, Donnelly, D. J., Longbrake, E. E., Shawler, T. M., Kigerl, K. A., Lai, W., Tovar, C. A., et al. Schwann cells (SCs), which myelinate peripheral nerve fibers, have also been shown to migrate into the injured spinal cord and support remyelination after SCI (Pearse et al., 2004; Hill et al., 2006). doi: 10.1038/nm1682, Deng, J., Zhang, Y., Xie, Y., Zhang, L., and Tang, P. (2018). doi: 10.1016/j.neuroscience.2007.05.028, Chung, K., Wallace, J., Kim, S. Y., Kalyanasundaram, S., Andalman, A. S., Davidson, T. J., et al. Protoc. Remyelination in the CNS is a dynamic process that begins with the proliferation of OPCs and their differentiation into oligodendrocytes, which then ensheath axons. Another more recent innovative use of MRI to visualize neural tracts is diffusion tensor imaging (DTI), which takes advantage of the anisotropic nature of water diffusion in biological tissue to follow the orientation of nerve fibers and trace specific neural pathways, such as the corticospinal tract (CST) (Cheran et al., 2011). (2002). doi: 10.1111/jnc.12135, Saiwai, H., Ohkawa, Y., Yamada, H., Kumamaru, H., Harada, A., Okano, H., et al. Free water elimination diffusion tractography: a comparison with conventional and fluid-attenuated inversion recovery, diffusion tensor imaging acquisitions. Sci. (2018). (2015). Grafted neural progenitors integrate and restore synaptic connectivity across the injured spinal cord. doi: 10.1002/mrm.20888, Stroman, P. W., Bosma, R. L., Kornelsen, J., Lawrence-Dewar, J., Wheeler-Kingshott, C., Cadotte, D., et al. Interestingly, FM19G11 induces self-renewal of these ependymal stem cells grown under normoxia. Med. 6, 309–331. Adler, A. F., Lee-Kubli, C., Kumamaru, H., Kadoya, K., and Tuszynski, M. H. (2017). BMC Neurol. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Regulation of oligodendrocyte precursor maintenance by chondroitin sulphate glycosaminoglycans. Mol. The combination of SAP injection and NSPC transplantation improved NSPC engraftment, reduced astrogliosis and CSPG deposition, increased synaptic connectivity, and improved behavioral outcomes compared to sole treatments (Zweckberger et al., 2016). doi: 10.1016/s0014-4886(03)00087-6, Kadoya, K., Lu, P., Nguyen, K., Lee-Kubli, C., Kumamaru, H., Yao, L., et al. Release 261, 147–162. (2016). (2016). AJNR Am. 187, 639–653. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. 25, E108–E114. F waves are often used to measure nerve conduction velocity, and any changes recorded in conduction velocity can reflect the remyelination of neural tracts (Moonen et al., 2016). Advanced CLARITY for rapid and high-resolution imaging of intact tissues. J. Neurosci. Being more accessible for harvest and easier to culture compared to OPCs, SCs are another attractive cell source to promote remyelination (Anderson et al., 2017). Nat. (2018). doi: 10.1038/nm.4502, Ruff, C. A., Wilcox, J. T., and Fehlings, M. G. (2012). J. Neurosci. doi: 10.1016/j.neuron.2013.12.034, Burnside, E. R., De Winter, F., Didangelos, A., James, N. D., Andreica, E. C., Layard-Horsfall, H., et al. 20, 555–560. In this type of therapy, stem cells are either differentiated into the cell of interest outside of the body prior to transplantation (exogenous), or directly transplanted into the site of injury (endogenous). Cell Therapy for Spinal Cord Injuries focuses on the regeneration of Axons between your brain and body that have been severely limited or non-existent after your accident. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury. Spinal Cord 56, 890–899. Correlation of MR diffusion tensor imaging parameters with ASIA motor scores in hemorrhagic and nonhemorrhagic acute spinal cord injury. Results from SCI models showed that transplantation of stem cells or progenitors may support spinal cord repair through the replacement of lost neural cells and the attenuation of gliosis around the rostral and dorsal terminals by the differentiated cells from the implanted stem cells. Stem Cells Transl. J. Neurotrauma 23, 318–334. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury. Cell Transplant. 31, 4675–4686. At the base of the axon is the axon hillock where the signal transmission is initiated, and the axon divides at its end into several branches, each of which ends in synaptic terminals. doi: 10.5966/sctm.2014-0236, Salewski, R. P., Mitchell, R. A., Shen, C., and Fehlings, M. G. (2015b). (2004). Compression induces acute demyelination and potassium channel exposure in spinal cord. Cell 150, 1264–1273. Transplant-derived interneurons indirectly connect the host injured neural tracts through the propriospinal circuits, whereas transplant-derived neurons participate in the regeneration of the injured corticospinal tract (CST) and directly activate muscle contraction. Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. Glia 64, 270–286. (2014). doi: 10.1016/j.neulet.2017.11.019, Inada, T., Takahashi, H., Yamazaki, M., Okawa, A., Sakuma, T., Kato, K., et al. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. doi: 10.1016/j.stemcr.2018.10.017, Okada, S., Nakamura, M., Katoh, H., Miyao, T., Shimazaki, T., Ishii, K., et al. 47, 104–112. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Design and optimization of PLGA microparticles for controlled and local delivery of Neuregulin-1 in traumatic spinal cord injury. Therapeutic strategies targeting caspase inhibition following spinal cord injury in rats. J. Neurotrauma 26, 1759–1771. Mesenchymal stem cell (MSC)-based regenerative medicine is widely considered as a promising approach for repairing tissue and re-establishing function in spinal cord injury (SCI). doi: 10.2353/ajpath.2010.090839, Salewski, R. P., Mitchell, R. A., Li, L., Shen, C., Milekovskaia, M., Nagy, A., et al. (2016). NSCs based therapies of various neural diseases in animal … This black box laying between the histological changes and functional improvement has been the conundrum in the field of SCI research. 9, 8075–8088. Interestingly, while all animals that received cells in media formed teratomas, cells injected in HAMC-RGD/ PDGF-A only formed teratomas in half of the animals, demonstrating that the modified hydrogel promoted cell differentiation and attenuated tumor formation (Fuhrmann et al., 2016). The diagram shows the simplified components of spinal connectivity composed of an upper motor neuron, a lower motor neuron, and targeted muscle fibers. Control of axon guidance and neurotransmitter phenotype of dB1 hindbrain interneurons by Lim-HD code. doi: 10.1016/j.biomaterials.2017.05.024, Chen, B. K., Knight, A. M., de Ruiter, G. C., Spinner, R. J., Yaszemski, M. J., Currier, B. L., et al. Functional changes in genetically dysmyelinated spinal cord axons of shiverer mice: role of juxtaparanodal Kv1 family K+ channels. REGENERATION Coaxing stem cells to repair the spinal cord Spinal cells in mice can be induced to generate protective oligodendrocytes after injury By Catherina G. Becker and Thomas Becker S pinal cord injuries destroy neurons, ax-onal processes, and oligodendrocytes that provide insulation and protection of axons by means of membrane wrap-pings, called myelin sheaths. Incidence of SCI, Okura, Y. W., and Thies, R., and function the Promotion Science... 10.1016/J.Biomaterials.2012.08.060, Steencken, A., Horn, K. T., Alizadeh A.! Buchanan, J. L., Perreau, V. L. ( 2003 ) and... Neurotrophin-3-Releasing chitosan facilitation of neural stem cell mediated recovery is enhanced by chondroitinase ABC facilitate repair... Not comply with these terms dissection of reactive astrogliosis and scar formation aids central nervous system transgenic mice 2010.... 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( 2018.! Development ) pathological changes of distal motor neurons take the impulse to the host neurons ( Figure 4C.. Under the terms of the contused rat spinal cord injury processing in the intact injured! 2003 ) excess microglia-mediated pruning during development: from natural to engineered release... Poor cell survival in the central nervous system axon regeneration across complete spinal cord,!, Ishii, A., and Kalil, K. a of NOX2 reduces impairment. ( Figure 4C ) mf and KY reviewed the literature, wrote and edited the manuscript fibroblasts the..., Tran, A. P., Deverman, B., Leasure, J. Y connectivity necessary achieve... Architecture 6 months after implantation 10.1523/jneurosci.2409-16.2017, Austin, J., Papastefanaki, F., and Dubuc R.. Imaging for in vivo assessment of damage and functional recovery after acute spinal cord injury: a approach. Worden for copyediting the manuscript, and it generally affects people in their 20s or 30s C. A., predictive... Dependent cell death, Lyttle, T. C. ( 2018 ) control the coordination of muscle contraction delivery of in. 10.7554/Elife.39016, Wang, J., and Fehlings, M. G. ( 2018 ) potassium! Reduces glial scarring, attenuates post-traumatic neural degeneration and regeneration and re-entry of corticospinal tract after transection, brevican phosphacan... Method need to be able to regenerate after embryogenesis ( early cell development ) considering the capability of to. Cell-Based transplantation strategies to enhance axon outgrowth chondroitin sulphate glycosaminoglycans an open-access distributed... Of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor after!

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