Many STEM121-positive/MBP-positive graft-derived myelin sheathes were observed around NF200-positive host axons. 22, 479–487. 38, 745–753. doi: 10.1073/pnas.1804735115, Raposo, C., Graubardt, N., Cohen, M., Eitan, C., London, A., Berkutzki, T., et al. Disrupted blood vessels cause severe hemorrhage (Saiwai et al., 2010; Yokota et al., 2016) and allow infiltration of inflammatory cells including neutrophils, monocytes/macrophages, T cells, and B cells into the spinal cord tissue (Ankeny et al., 2009; Beck et al., 2010; Saiwai et al., 2013; Raposo et al., 2014) that release inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and IL-6 (Kumamaru et al., 2012; Nguyen et al., 2012). With the large cavity forming after SCI being an obstacle for regenerating axons, there have been many attempts to implant constructs into the cavity to provide axons with a substrate on which to grow and to restore tissue continuity across the trauma zone. 30, 2989–3001. (2015). doi: 10.1038/nm.4066, Kaptanoglu, E., Caner, H., Solaroglu, I., and Kilinc, K. (2005). Biomaterials 138, 91–107. 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). Cell Death Differ. The ongoing progress seen in neural tracing procedures, electrophysiological techniques, as well as imaging hardware and software has improved our understanding of the plasticity of neural circuits following SCI and the importance of propriospinal circuits in the restoration of neural connectivity, but at the same time, the increasing knowledge emphasizes our lack of control on the processes that govern the rewiring of pathways. We will focus on the capacity of these strategies to facilitate the regeneration of neural connectivity necessary to achieve meaningful functional recovery after SCI. Changes in pain processing in the spinal cord and brainstem after spinal cord injury characterized by functional magnetic resonance imaging. (2018). 10, 1860–1896. doi: 10.1016/j.expneurol.2014.01.013, Faulkner, J. R., Herrmann, J. E., Woo, M. J., Tansey, K. E., Doan, N. B., and Sofroniew, M. V. (2004). Acute cervical traumatic spinal cord injury: MR imaging findings correlated with neurologic outcome–prospective study with 100 consecutive patients. Natl. (2013). 3D cell cultures; neural stem cells; self-assembling peptides; spinal cord injury; nervous tissue engineering; Three-dimensional cell culture systems are gaining interest in the scientific community because of the number of potential applications in biotechnology ().Researchers stimulated induced pluripotent stem cells or embryonic stem cells to self-organize under various conditions to … Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival. PLoS One 7:e37589. J. Neurosci. Many biomaterial substrates have been studied as candidate scaffolds for the treatment of SCI: collagen, laminin, fibrin matrices, fibronectin, hyaluronan-methylcellulose, chitosan, agarose, alginate, methylcellulose, poly(2-hydroxyethyl methacrylate) or pHEMA, poly(N-(2-hydroxypropyl) methacrylamide) or pHPMA, and poly(lactic-co-glycolic) acid or PLGA. doi: 10.1016/j.immuni.2018.04.016, Filli, L., Engmann, A. K., Zorner, B., Weinmann, O., Moraitis, T., Gullo, M., et al. (2013). Clin. Spinal cord-derived NSPCs suspended in a fibrin matrix containing brain-derived neurotrophic factor, basic fibroblast growth factor, vascular endothelial growth factor, and a calpain inhibitor were loaded into the scaffolds and inserted into a rat thoracic cord transection lesion. doi: 10.1016/j.celrep.2013.03.031, Eftekharpour, E., Karimi-Abdolrezaee, S., Wang, J., El Beheiry, H., Morshead, C., and Fehlings, M. G. (2007). doi: 10.1016/j.jconrel.2017.06.030, Satkunendrarajah, K., Karadimas, S. K., Laliberte, A. M., Montandon, G., and Fehlings, M. G. (2018). Remyelination reporter reveals prolonged refinement of spontaneously regenerated myelin. Engrafted neural stem/progenitor cells promote functional recovery through synapse reorganization with spared host neurons after spinal cord injury. They are planning to conduct a first-in-human study of an induced pluripotent stem cell-based intervention, for subacute spinal cord injury. Nat. J. Spinal Cord Med. OPCs are predominantly quiescent in the healthy CNS, but in response to injury they proliferate and differentiate into mature oligodendrocytes, which contribute to remyelination (Assinck et al., 2017). 23, 818–828. IFN-gamma-dependent activation of the brain’s choroid plexus for CNS immune surveillance and repair. Neurol. J. Neurosci. Acad. J. Pathol. The chitosan scaffold effectively prevented infiltration of inflammatory cells, attracted endogenous neural stem cells to proliferate, migrate, and differentiate into neurons, and facilitated the reorganization of neural relay networks to transmit ascending and descending neural signals (Yang et al., 2015). Electrocardiographic abnormalities in the early stage following traumatic spinal cord injury. 25, 4694–4705. doi: 10.1371/journal.pbio.0060182, Min, K. J., Jeong, H. K., Kim, B., Hwang, D. H., Shin, H. Y., Nguyen, A. T., et al. Control of axon guidance and neurotransmitter phenotype of dB1 hindbrain interneurons by Lim-HD code. (2017). (2018). Acad. Neurobiol. 34, 16031–16045. 6:e182. 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. (2018). Being the product of chemical bioengineering, synthetic biomaterials allow for greater product consistency and tunable properties compared to natural ones (Pakulska et al., 2015, 2016a). doi: 10.1523/jneurosci.21-24-09814.2001, Yang, B., Treweek, J. This recognition of the personal and social costs of SCI has fostered extensive basic research into the pathology of the injured spinal cord and treatment strategies for SCI. Involvement of mitochondrial signaling pathways in the mechanism of Fas-mediated apoptosis after spinal cord injury. doi: 10.1016/j.nbd.2017.05.009, Wilcox, J. T., Satkunendrarajah, K., Zuccato, J. (2018). For people with spinal cord injuries, stem cells could prevent further cell death, stimulate cell growth from the existing cells and even replace the injured cells, restoring the communication channels between the body and the brain. The axons from the engrafted NSPCs formed synapses that led to improved electrophysiological and functional improvements (Lu et al., 2012). Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery. doi: 10.1634/stemcells.2005-0249, Keirstead, H. S., Nistor, G., Bernal, G., Totoiu, M., Cloutier, F., Sharp, K., et al. They state that the approval for the research was based on a small, poorly designed clinical trial. 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). Therefore, it is becoming increasingly more frequent to combine stem cell transplantation with other strategies that would enhance the effect of the transplanted cells (Ruff et al., 2012). Phenotypic characterization of speed-associated gait changes in mice reveals modular organization of locomotor networks. Med. 14, 69–74. The recent advances in neuronal tracers have bestowed researchers with the means to investigate the reorganization of neural networks after SCI and to better appreciate the underlying mechanisms that govern the regeneration of injured spinal cords (Kerschensteiner et al., 2005). Mol. J. Neurosci. Indeed, infusion of the growth factors EGF and FGF2 into the central canal was shown to increase the proliferation of ependymal cells and improve functional recovery after SCI, demonstrating the potential of ependymal cell manipulation as an alternative to exogenous stem cell transplantation (Kojima and Tator, 2002). Ann. Neural stem cells (NSCs) have gained increasing attention as promising regenerative therapy of SCI. When this processing of components through the autophagy system, or autophagy flux, is blocked or overrun by components awaiting processing, the accumulation of dysfunctional autophagosomes damages cells and triggers death (Lipinski et al., 2015). (2015). Comprehensive monosynaptic rabies virus mapping of host connectivity with neural progenitor grafts after spinal cord injury. doi: 10.1089/ars.2015.6306, Liu, M., Wu, W., Li, H., Li, S., Huang, L. T., Yang, Y. Q., et al. In vivo tracing of neural tracts in the intact and injured spinal cord of marmosets by diffusion tensor tractography. Exp. Neurol. doi: 10.1002/jcp.22845, Kunis, G., Baruch, K., Rosenzweig, N., Kertser, A., Miller, O., Berkutzki, T., et al. (2016). doi: 10.1016/j.stem.2010.07.014, Beck, K. D., Nguyen, H. X., Galvan, M. D., Salazar, D. L., Woodruff, T. M., and Anderson, A. J. (2013). eLife 7:e39016. These studies reveal that NSPC-derived myelin is essential to the remyelination process after SCI, and demonstrate the important role that remyelination plays in the functional recovery brought about by stem cell transplantation strategies to treat SCI. Impact of multimodal intraoperative monitoring during surgery for spine deformity and potential risk factors for neurological monitoring changes. J. Neurotrauma 34, 2950–2963. Much has been uncovered concerning the function of reactive astrocytes in SCI, and research is ongoing on how to enhance their beneficial roles while minimizing their deleterious effects. 30, 1001–1012. 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). https://t.co/l0skMjt01K, This interesting study looks at aiming to repair pathogenic allele-specific single-nucleotide mutations using a sin… https://t.co/2TN5FN8yYo. Brain Res. Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. (2010). Restorative effects of human neural stem cell grafts on the primate spinal cord. Kuang, R. Z., and Kalil, K. (1990). The term “regeneration” has been used for decades in the field of central nervous system research (Worcester, 1898), but it may be helpful to review what regeneration entails in the recovery process from SCI. (2011). Spinal Cord 56, 890–899. The autophagy pathway is closely linked to endoplasmic reticulum stress, which also plays a role in maintaining cellular homeostasis and triggers apoptosis if endoplasmic reticulum stress exceeds the capacity of its processing mechanism (Kuroiwa et al., 2014). (2014). Loss of postsynaptic GABA(A) receptor clustering in gephyrin-deficient mice. Mater. doi: 10.1038/nmeth999, Wilcox, J. T., Satkunendrarajah, K., Nasirzadeh, Y., Laliberte, A. M., Lip, A., Cadotte, D. W., et al. Furthermore, refractory substrates generated in the injured spinal cord inhibit spontaneous recovery. Selected studies using a combinatorial therapy comprised of neural stem cell transplantation with a biomaterial containing neuroprotective agents. J. 34, 1231–1243. Science 333, 238–242. (2017). Spine 44, 479–487. doi: 10.1523/jneurosci.3354-07.2007, Furlan, J. C., Verocai, F., Palmares, X., and Fehlings, M. G. (2016). 8, 260–270. These biomaterial depots were prepared using diblock copolypeptide hydrogels that are biocompatible with the CNS, biodegrade over several weeks, and provide delivery of bioactive growth factors for at least 2 weeks (Yang et al., 2009; Song et al., 2012). It will happen. 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. doi: 10.1016/j.neuron.2014.07.027. These attempts started as oriented structures to act as bridges for growing axons, but have since evolved to secrete factors that enhance tissue growth and vascularization, deliver drugs, and act as a vehicle to deliver cells into the lesion (Elliott Donaghue et al., 2014). Global prevalence and incidence of traumatic spinal cord injury. J. Neurotrauma 33, 278–289. Brain 135(Pt. doi: 10.1089/neu.2017.5012, Li, X., Xiao, Z., Han, J., Chen, L., Xiao, H., Ma, F., et al. Although reactive astrocytes have been implicated with most of the inhibitive effects of scarring after SCI, studies have demonstrated the inhibitive effects of a fibrotic scar comprised of a dense extracellular matrix made up of fibronectin, collagen, and fibroblasts. U.S.A. 112, 13354–13359. doi: 10.1002/mrm.20888, Stroman, P. W., Bosma, R. L., Kornelsen, J., Lawrence-Dewar, J., Wheeler-Kingshott, C., Cadotte, D., et al. The tumorigenicity of iPS cells was reviewed in a recent report (Deng et al., 2018), and methods to eliminate iPS cell-derived tumors are being refined (Kojima et al., 2019). 9, 1682–1697. However, one of the issues that needs to be addressed is tumorigenicity, which is a potential problem with all stem cell transplantations, but it has been most closely studied in iPS cell lines due to its imminent clinical application. doi: 10.1016/j.conb.2014.03.010, Lu, P., Wang, Y., Graham, L., McHale, K., Gao, M., Wu, D., et al. (2012). 31, 9910–9922. (2017). The results go against an existing belief that corticospinal neurons lack the internal mechanisms to be able to regenerate in this way. (2016a). Epidemiological state, predictors of early mortality, and predictive models for traumatic spinal cord injury: a multicenter nationwide cohort study. Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model. (2016). J. Neurosci. Adler, A. F., Lee-Kubli, C., Kumamaru, H., Kadoya, K., and Tuszynski, M. H. (2017). Cell Rep. 3, 1199–1212. doi: 10.5966/sctm.2015-0295, Bao, X., Wei, J., Feng, M., Lu, S., Li, G., Dou, W., et al. (C) Immunoelectron microscopy images show synapses formed between host and graft-derived neurons after the combinatorial treatment. The primary and secondary injury mechanisms lead to inflammation, hemorrhage, apoptosis, and necrosis. EMG signals may be useful to verify synaptic connectivity by examining the conduction of electrical impulses through the lesion, but currently cannot be used to examine the regeneration of specific pathways in spinal cord circuits. 188, 51–70. Neurol. Immediately after injury, astrocytes proliferate and organize around the edges of the lesion to wall off the damaged area from the surrounding healthy tissue. The initial traumatic event, which may or may not accompany fractures and/or a dislocation of the vertebral column, results in the primary injury through mechanical compression, contusion, stretching, or kinking of the spinal cord (Sekhon and Fehlings, 2001). (2007). 227, 1335–1346. (2015). 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). Spine 8, 365–375. 29, 114–131. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system. Med. 25, 263–269. (2009). The later H-wave, or H-reflex, is a compound EMG response in the muscle elicited by synaptic activation of motor neurons through muscle afferents and is regarded as a surrogate for spasticity after SCI. 22, 421–435. Riluzole improves outcome following ischemia-reperfusion injury to the spinal cord by preventing delayed paraplegia. Copyright © 2019 Katoh, Yokota and Fehlings. 27, 11991–11998. The results of this study suggest that transplanted exogenous neural stem cells may induce neurogenesis in the spinal cord ependymal niche and also promote survival of the newly generated host neurons, which is similar to the neurogenesis induced in the brain subventricular zone by NSPC and mesenchymal stem cell grafts (Bao et al., 2011; Jin et al., 2011). CSPGs have been shown to repel regenerating axons and also prevent oligodendrocyte maturation and remyelination (Karus et al., 2016). J. Neurosci. Retrograde neuronal tracing with a deletion-mutant rabies virus. Reson. Using immunoelectron microscopy, they also revealed that immunogold-labeled differentiated graft-derived neurons formed synaptic connectivity with host neurons (Figure 4C). This study demonstrated that with an appropriate combinatorial therapy including ChABC and stem cell transplantation, regeneration in the chronically injured spinal cord is also possible. (2012). (2007). J. Neurotrauma 34, 1209–1226. In both traumatic (C2 hemisection) and non-traumatic (cervical myelopathy) SCI models, respiratory control shifted from phrenic motor neurons that normally control diaphragm motion to mid-cervical excitatory interneurons, which are normally not essential for the maintenance of breathing in healthy animals. 38, 5399–5414. Brain 136(Pt. doi: 10.1523/jneurosci.2524-13.2013, Sofroniew, M. V. (2009). 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). (2012). doi: 10.1038/nature12107, Courtine, G., Song, B., Roy, R. R., Zhong, H., Herrmann, J. E., Ao, Y., et al. Traumatic injury to the spinal cord can be caused by compressions, lacerations, and contusions, which lead to a spectrum of neurological symptoms depending on the level and the severity of the injury such as motor/sensory dysfunction, autonomic deficits, neuropathic pain, autonomic dysreflexia, and bowel/bladder dysfunction (Furlan et al., 2016; Moonen et al., 2016; Stroman et al., 2016). Local BDNF delivery to the injured cervical spinal cord using an engineered hydrogel enhances diaphragmatic respiratory function. doi: 10.1016/j.neuroscience.2014.01.059, Xu, L., Mahairaki, V., and Koliatsos, V. E. (2012). doi: 10.1016/j.jneumeth.2016.06.004, Moonen, G., Satkunendrarajah, K., Wilcox, J. T., Badner, A., Mothe, A., Foltz, W., et al. . Additional grant support was from the Krembil Foundation (to MF and KY). Intact-brain analyses reveal distinct information carried by SNc dopamine subcircuits. B., Gabitto, M. I., Rivard, A. F., Drobac, E., Machado, T. A., Miri, A., et al. (2017). doi: 10.1172/jci39780, Assinck, P., Duncan, G. J., Plemel, J. R., Lee, M. J., Stratton, J. 235, 78–90. (B) The diagram shows the pathophysiological events in the chronic phase of SCI. (2018a). Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. J. Neurosurg. The microenvironment of the SCI lesion is inhibitive to regeneration, and biomaterial scaffolds are implanted in the hopes of improving the lesion into a more growth-supportive environment that would support endogenous neurogenesis, axonal sprouting, and neural plasticity. doi: 10.1093/brain/awy158, Busch, S. A., Horn, K. P., Silver, D. J., and Silver, J. These stem cells are derived from adult skin cells. Although the pathological mechanisms underlying syringomyelia progression in CNS trauma is not completely understood, the process of posttraumatic cavitation is found in both humans and mammals. doi: 10.1016/j.neulet.2017.11.019, Inada, T., Takahashi, H., Yamazaki, M., Okawa, A., Sakuma, T., Kato, K., et al. Human spinal oligodendrogenic neural progenitor cells promote functional recovery after spinal cord injury by axonal remyelination and tissue sparing. J. Neurochem. Mechanistic insights into posttraumatic syringomyelia based on a novel in vivo animal model. (2012). doi: 10.1179/2045772314y.0000000224, Liu, Y., Ye, H., Satkunendrarajah, K., Yao, G. S., Bayon, Y., and Fehlings, M. G. (2013). High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury. These cells are typically harvested from bone marrow and can be used to prevent inflammatory … (2018). Neurol. doi: 10.1038/nm.4354, Hawryluk, G. W., Spano, S., Chew, D., Wang, S., Erwin, M., Chamankhah, M., et al. 10 Because whilst the research is still in its infancy, legitimate trials are showing promising results. Proc. Regeneration of nerve fibres in the central nervous system. Neuron 68, 9–18. While we recognize that neural stem cells, neural progenitor cells, and neural precursor cells are, strictly speaking, different cell populations, we also believe that most cell transplants are a mix of these cells. doi: 10.1523/jneurosci.0076-14.2014, Robins-Steele, S., Nguyen, D. H., and Fehlings, M. G. (2012). Axonal growth and connectivity from neural stem cell grafts in models of spinal cord injury. 11), 3427–3440. ChABC was administered with the intent to degrade CSPGs and also to maintain the oligodendrocytes profile of the drOPCs (Karimi-Abdolrezaee et al., 2012). View all Differentiated oligodendrocytes remyelinate denuded axons. That hope was gradually replaced with mounting frustration when neuroprotective drugs, cell transplantation, and strategies to enhance remyelination, axonal regeneration, and neuronal plasticity demonstrated significant improvement in animal models of SCI but did not translate into a cure in human patients. doi: 10.1523/jneurosci.3214-17.2018, Tran, A. P., Warren, P. M., and Silver, J. New Stem Cells Could be Universally Transplanted, 5 Groundbreaking Regenerative Medicine Clinical Trials, The Link Between Honey Bees and Stem Cells, Stem Cell Therapy Could Help Treat Rheumatoid Arthritis, A fascinating read about a promising cell therapy for RPE (Retinal Pigment Epithelium) degeneration such as in age… https://t.co/4UkqBClZKq, An interesting article discussing a newly formed joint undertaking in Morphological Profiling with Cell Painting 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). 37, 4658–4660. doi: 10.1038/nm.3520, Burda, J. E., and Sofroniew, M. V. (2014). More than two decades ago, optimism prevailed with the discovery of molecules in mature CNS that inhibited neurite growth. J. Neurophysiol. doi: 10.1523/jneurosci.3189-11.2012, Wu, Y., Satkunendrarajah, K., and Fehlings, M. G. (2014). doi: 10.1002/cne.21771, Hoy, A. R., Kecskemeti, S. R., and Alexander, A. L. (2015). Spinal cord injury (SCI) affects millions of people worldwide, and results in the loss of neurons and limited recovery of functions. 207, 203–217. With systemic and localized inflammatory reactions persisting from the acute to chronic phase of SCI (Ulndreaj et al., 2017; Badner et al., 2018; Hong et al., 2018), interventions that modify inflammation hold promise as a means to reduce secondary damage after SCI (Nguyen et al., 2012; Badner et al., 2016), and modulating the phenotypes of the infiltrating macrophages may be a therapeutic strategy to promote functional recovery after SCI. J. Comp. The processes occurring within the injured spinal cord can be divided according to the elapsed time from the precipitating injury into acute (<48 h), subacute (48 h to 14 days), intermediate (14 days to 3 months), and chronic phases (>3 months) (Aimone et al., 2004; Shechter et al., 2009; Chamankhah et al., 2013; Moghaddam et al., 2015). Schwann cells engineered to express the cell adhesion molecule L1 accelerate myelination and motor recovery after spinal cord injury. doi: 10.1016/j.neuroscience.2009.12.010, Tomer, R., Ye, L., Hsueh, B., and Deisseroth, K. (2014). Methods 4, 47–49. Laboratory investigation. Recent advances in stem cell engineering have led to the development of directly reprogrammed NSPCs from human fibroblasts, blood cells, and mesenchymal cells, and they have demonstrated their potential to promote axonal remyelination and tissue sparing in mammal SCI models (Nagoshi et al., 2018). Brain Res. Encapsulation-free controlled release: electrostatic adsorption eliminates the need for protein encapsulation in PLGA nanoparticles. 125, 74–88. J. Neurosci. doi: 10.1074/jbc.M806630200, Proskuryakov, S. Y., Konoplyannikov, A. G., and Gabai, V. L. (2003). (2012). doi: 10.1089/neu.2009.0934, Stieltjes, B., Klussmann, S., Bock, M., Umathum, R., Mangalathu, J., Letellier, E., et al. (2011). The animal studies and in vitro studies provide a solid platform to proceed to well-designed human studies on stem cell transplantation for spinal cord injury. 196, 390–400. In order to sidestep some of the disadvantages of ChABC, recent studies are looking into gene therapies to engineer ChABC expression in the injured spinal cord (James et al., 2015; Burnside et al., 2018). An examination of the mechanisms by which neural precursors augment recovery following spinal cord injury: a key role for remyelination. Although modifications of the grafting technique and immunosuppression were required, the human NSPCs grafted into the monkey spinal cord extended long axons through the host white matter that formed synapses in the caudal lumbar gray matter, and led to improved forelimb function (Rosenzweig et al., 2018). 257, 186–204. Cell-based transplantation strategies to promote plasticity following spinal cord injury. (2008). B., Kulkarni, R. P., Deverman, B. E., Chen, C. K., Lubeck, E., et al. With the aid of a stereotaxic apparatus to guide the exact site of the injection, the tracer is injected into selected areas of the brain for anterograde transport and into peripheral organs or spinal segments for retrograde transport, and analyzed in histological sections after a specific period (Chen et al., 2009; Mondello et al., 2016). Neurol. Neurons have cell bodies, dendrites that receive signals, and axons that transmit signals. doi: 10.1002/adma.201502767, Papastefanaki, F., Chen, J., Lavdas, A. Sci. CSPG inhibition has been shown to be mediated by two members of the Leukocyte Common Antigen Related (LAR) phosphatase subfamily, protein tyrosine phosphatase σ (PTPσ) and LAR, and PTPσ receptors have been shown to mediate the regulation of oligodendrocyte differentiation and apoptosis by CSPGs in the injured spinal cord (Fisher et al., 2011; Dyck et al., 2018). Synapse contain tiny vesicles filled with chemicals called neurotransmitters reduces locomotor impairment, inflammation and... From the site of spinal cord of caspase-3 activation and oligodendrocyte integrity in spinal cord injury mice. Recovery following spinal cord injury characterized by functional magnetic resonance imaging for in vivo imaging of sprouting. Practical Barriers and new cell source for cell-based therapies ) dynamics in manganese-enhanced MRI ( MEMRI ): channel-mediated. Lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal injury... 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