Spinal shock revisited: a four-phase model. Spinal cord. Motor classification of spinal cord injuries with mobility, morbidity and recovery indices. Am Surg. Forecasting motor recovery after cervical spinal cord injury: value of MR imaging.
Outcome of decompression surgery for cervical spinal cord injury without bone and disc injury in patients with spinal cord compression: a multicenter prospective study. Resnick D, Niwayama G. Radiographic and pathologic features of spinal involvement in diffuse idiopathic skeletal hyperostosis DISH.
AOSpine subaxial cervical spine injury classification system. Eur Spine J. Spinal cord injury without radiographic abnormality in adults. Can magnetic resonance imaging reflect the prognosis in patients of cervical spinal cord injury without radiographic abnormality? Kanda Y. Bone Marrow Transpl. Subacute T1-low intensity area reflects neurological prognosis for patients with cervical spinal cord injury without major bone injury.
Magnetic resonance imaging in acute cervical spinal cord injury: a correlative study on spinal cord changes and 1 month motor recovery. Traumatic epidural hematoma of the cervical spine: diagnosis with magnetic resonance imaging. Case report. J Neurosurg. The role of magnetic resonance imaging in the management of acute spinal cord injury. Prognostic significance of magnetic resonance imaging in the acute phase of cervical spine injury.
Emergency magnetic resonance imaging of cervical spinal cord injuries: clinical correlation and prognosis. Predicting neurologic recovery in cervical spinal cord injury with postoperative MR imaging. Spine Phila Pa Acute spinal cord injury. A study using physical examination and magnetic resonance imaging. Clinical and magnetic resonance imaging correlation in acute spinal cord injury.
Shimada K, Tokioka T. Sequential MR studies of cervical cord injury: correlation with neurological damage and clinical outcome.
Soft-tissue damage and segmental instability in adult patients with cervical spinal cord injury without major bone injury. Acute hyperglycemia impairs functional improvement after spinal cord injury in mice and humans. Sci Transl Med.
Recovery of ambulation in motor-incomplete tetraplegia. The case for early treatment of dislocations of the cervical spine with cord involvement sustained playing rugby. J Bone Jt Surg Br. Traumatic central cord syndrome: results of surgical management. Early surgical intervention may facilitate recovery of cervical spinal cord injury in DISH. J Orthop Surg Hong Kong. How much time is necessary to confirm the diagnosis of permanent complete cervical spinal cord injury?
Motor power differences within the first two weeks post-SCI in cervical spinal cord-injured quadriplegic subjects. Motor and sensory recovery following complete tetraplegia. Motor and sensory recovery following incomplete tetraplegia. Locomotor control in macaque monkeys. The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury.
Exp Neurol. Raineteau O, Schwab ME. When the same cells were transplanted in fibrin matrix containing a cocktail of growth factors brain-derived neurotrophic factor, neurotrophin-3, glial-cell-line-derived neurotrophic factor, epidermal growth factor, basic fibroblast growth factor, acidic fibroblast growth factor, hepatocyte growth factor, insulin-like growth factor, platelet-derived growth factor, vascular endothelial growth factor, and a calpain inhibitor , the transplanted NSPCs filled the lesion gap and demonstrated robust axonal growth caudally into the host spinal cord.
The axons from the engrafted NSPCs formed synapses that led to improved electrophysiological and functional improvements Lu et al. A following study that examined the regeneration of the corticospinal tract CST by transplanting NSPCs and the growth cocktail-enhanced fibrin matrix into a similar rat transection model demonstrated robust CST axon regeneration across the lesion that formed functional synapses and led to improved forelimb function.
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. With the aim of generating translational data, the group then studied the effects of transplanting human spinal cord—derived NSPCs and the growth cocktail-enhanced fibrin matrix into sites of cervical SCI in rhesus monkeys.
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.
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. The transplanted NSPCs survived and filled the scaffold channels at 1 month, and the scaffolds maintained their 3D architecture 6 months after implantation.
Host axons regenerated into the scaffolds and formed synapses with NSPCs in the scaffold, while engrafted NSPCs extended axons into the host spinal cord and restored synaptic transmission, leading to electrophysiological and functional improvements. These studies show that with the appropriate combination of optimally engineered stem cells, scaffolds, and growth factors, the hostile environment of the SCI lesion can be improved and neural cells of the spinal cord can be coaxed into a state of regeneration.
Especially for the treatment of chronic SCI, a combinatorial approach is believed to be the only possible avenue to reactivate the regenerative processes and gain functional improvements. 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.
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 transplanted drOPCs enhanced synapse formation, promoted remyelination of host axons, and improved functional recovery Nori et al. They found that graft-derived cells formed a MBP-positive myelin sheath and enwrapped host spared axons in the chronically injured spinal cord Figures 4A,B.
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. Figure 4. Combinatorial treatment of stem cells and biomaterials containing ChABC elicits remyelination and synaptic reorganization.
C Immunoelectron microscopy images show synapses formed between host and graft-derived neurons after the combinatorial treatment. Presynaptic and postsynaptic structures indicate transmission from host neurons to graft-derived neuron left image , and from graft-derived neurons to host neurons right image. Annotated H indicates host neurons, and G indicates graft-derived neurons. Arrowheads indicate postsynaptic density. Figure altered with permission from Nori et al. Human oligodendrogenic neural progenitor cells delivered with chondroitinase ABC facilitate functional repair of chronic spinal cord injury 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.
By modulating inflammation, repopulating lost neural cells through transplantation, improving the local environment by implanting biomaterial scaffolds with growth factors, and implementing strategies to break down the inhibitory barriers, impressive recovery has been demonstrated in animal models of SCI. Yet it is important to keep in mind that all interventions must bring about an improvement in neural connectivity for any meaningful improvement to occur.
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.
Since aberrant rewiring has been implicated in mechanical allodynia, we must learn how to establish control of plasticity and not just blindly promote it. As more SCI studies begin to examine changes in spinal cord connectivity and the mechanisms underlying the rewiring of circuits and synapses, therapies that harness and enhance plasticity to promote the recovery from SCI will hopefully be developed in the near future.
HK and KY reviewed the literature, wrote and edited the manuscript, and finalized and approved the manuscript. MF conceived the frame and reviewed, edited, finalized, and approved the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. We would like to thank Dr. Tim Worden for copyediting the manuscript. We would also like to thank all the investigators who contributed to the establishment of therapeutic strategies for spinal cord injury utilizing biomaterials or stem cell transplantation over the years and apologize to those investigators whose work is not cited here due to the space limitations.
Adler, A. Comprehensive monosynaptic rabies virus mapping of host connectivity with neural progenitor grafts after spinal cord injury. Stem Cell Reports 8, — Aimone, J. Spatial and temporal gene expression profiling of the contused rat spinal cord. Anderson, K. Safety of Autologous human Schwann cell transplantation in subacute thoracic spinal cord injury. Neurotrauma 34, — Anderson, M. Astrocyte scar formation aids central nervous system axon regeneration.
Nature , — Required growth facilitators propel axon regeneration across complete spinal cord injury. Andrews, E. Alterations in chondroitin sulfate proteoglycan expression occur both at and far from the site of spinal contusion injury. Ankeny, D. B cells produce pathogenic antibodies and impair recovery after spinal cord injury in mice. Assinck, P.
Myelinogenic plasticity of oligodendrocyte precursor cells following spinal cord contusion injury. Austin, J. The relationship between localized subarachnoid inflammation and parenchymal pathophysiology after spinal cord injury.
Neurotrauma 29, — The effects of intrathecal injection of a hyaluronan-based hydrogel on inflammation, scarring and neurobehavioural outcomes in a rat model of severe spinal cord injury associated with arachnoiditis.
Biomaterials 33, — Backx, A. Quality of life, burden and satisfaction with care in caregivers of patients with a spinal cord injury during and after rehabilitation. Spinal Cord 56, — Badhiwala, J. Time is spine: a review of translational advances in spinal cord injury. Spine 30, 1— Badner, A.
Splenic involvement in umbilical cord matrix-derived mesenchymal stromal cell-mediated effects following traumatic spinal cord injury. Neuroinflammation Early intravenous delivery of human brain stromal cells modulates systemic inflammation and leads to vasoprotection in traumatic spinal cord injury. Stem Cells Transl. Bao, X. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats.
Brain Res. Baptiste, D. Pharmacological approaches to repair the injured spinal cord. Neurotrauma 23, — Bareyre, F. Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury. The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats.
Barnabe-Heider, F. Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell 7, — Beck, K. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment.
Brain Pt. Bedenk, B. Neuroimage , — Bellardita, C. Phenotypic characterization of speed-associated gait changes in mice reveals modular organization of locomotor networks. Bikoff, J. Spinal inhibitory interneuron diversity delineates variant motor microcircuits. Cell , — Bonner, J. Grafted neural progenitors integrate and restore synaptic connectivity across the injured spinal cord. Bradbury, E. Chondroitinase ABC promotes functional recovery after spinal cord injury.
Breckwoldt, M. Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo. Burda, J. Reactive gliosis and the multicellular response to CNS damage and disease. Neuron 81, — Burnside, E. Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury. Brain , — Busch, S. Overcoming macrophage-mediated axonal dieback following CNS injury. Bush, T. Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice.
Neuron 23, — Cao, Q. Transplantation of ciliary neurotrophic factor-expressing adult oligodendrocyte precursor cells promotes remyelination and functional recovery after spinal cord injury. Casha, S. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat.
Neuroscience , — FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury. Results of a phase II placebo-controlled randomized trial of minocycline in acute spinal cord injury.
Chamankhah, M. Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model. BMC Genomics Chedly, J. Physical chitosan microhydrogels as scaffolds for spinal cord injury restoration and axon regeneration. Biomaterials , 91— Chen, B. Axon regeneration through scaffold into distal spinal cord after transection. Neurotrauma 26, — Cheran, S.
Correlation of MR diffusion tensor imaging parameters with ASIA motor scores in hemorrhagic and nonhemorrhagic acute spinal cord injury. Neurotrauma 28, — Chu, G.
The p75 neurotrophin receptor is essential for neuronal cell survival and improvement of functional recovery after spinal cord injury. Chung, K. Structural and molecular interrogation of intact biological systems. Courtine, G.
Recovery of supraspinal control of stepping via indirect propriospinal relay connections after spinal cord injury. Deng, J. Stem Cells Int. Deng, L. 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.
Dhall, S. Motor evoked potentials correlate with magnetic resonance imaging and early recovery after acute spinal cord injury. Neurosurgery 82, — Dias, D. Reducing pericyte-derived scarring promotes recovery after spinal cord injury.
Donnelly, D. Dyck, S. LAR and PTPsigma receptors are negative regulators of oligodendrogenesis and oligodendrocyte integrity in spinal cord injury. Glia 67, — Easley-Neal, C. Late recruitment of synapsin to nascent synapses is regulated by Cdk5. Cell Rep. Eftekharpour, E. Myelination of congenitally dysmyelinated spinal cord axons by adult neural precursor cells results in formation of nodes of Ranvier and improved axonal conduction.
Elliott Donaghue, I. Cell and biomolecule delivery for tissue repair and regeneration in the central nervous system. Release , — Evans, T. High-resolution intravital imaging reveals that blood-derived macrophages but not resident microglia facilitate secondary axonal dieback in traumatic spinal cord injury.
Faulkner, J. Reactive astrocytes protect tissue and preserve function after spinal cord injury. Fehlings, M. Rho inhibitor VX in acute traumatic subaxial cervical spinal cord injury: design of the spinal cord injury rho inhibition investigation SPRING clinical trial. Neurotrauma 35, — A clinical practice guideline for the management of patients with acute spinal cord injury: recommendations on the role of baseline magnetic resonance imaging in clinical decision making and outcome prediction.
Global Spine J. Feng, B. Impact of multimodal intraoperative monitoring during surgery for spine deformity and potential risk factors for neurological monitoring changes.
Spinal Disord. Filipello, F. The microglial innate immune receptor TREM2 is required for synapse elimination and normal brain connectivity. Immunity 48, — Filli, L. Bridging the gap: a reticulo-propriospinal detour bypassing an incomplete spinal cord injury.
Fisher, D. Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. Floriddia, E. Fuhrmann, T. Injectable hydrogel promotes early survival of induced pluripotent stem cell-derived oligodendrocytes and attenuates longterm teratoma formation in a spinal cord injury model.
Biomaterials 83, 23— Fujiyoshi, K. In vivo tracing of neural tracts in the intact and injured spinal cord of marmosets by diffusion tensor tractography. Furlan, J. Electrocardiographic abnormalities in the early stage following traumatic spinal cord injury. Spinal Cord 54, — Galluzzi, L. Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death Cell Death Differ.
Geisler, F. Recovery of motor function after spinal-cord injury—a randomized, placebo-controlled trial with GM-1 ganglioside. Ghosh, B. Local BDNF delivery to the injured cervical spinal cord using an engineered hydrogel enhances diaphragmatic respiratory function.
Golden, K. Transduced Schwann cells promote axon growth and myelination after spinal cord injury. Goritz, C. A pericyte origin of spinal cord scar tissue. Science , — Haggerty, A. Biomaterials for spinal cord repair. Hara, M. Interaction of reactive astrocytes with type I collagen induces astrocytic scar formation through the integrin-N-cadherin pathway after spinal cord injury. Hawryluk, G. An examination of the mechanisms by which neural precursors augment recovery following spinal cord injury: a key role for remyelination.
Cell Transplant. Herrmann, J. STAT3 is a critical regulator of astrogliosis and scar formation after spinal cord injury. Hill, C. Labeled Schwann cell transplantation: cell loss, host Schwann cell replacement, and strategies to enhance survival.
Glia 53, — Hong, J. Level-specific differences in systemic expression of pro- and anti-inflammatory cytokines and chemokines after spinal cord injury. Horn, K. Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions.
Hou, S. Plasticity of lumbosacral propriospinal neurons is associated with the development of autonomic dysreflexia after thoracic spinal cord transection.
Hoy, A. Free water elimination diffusion tractography: a comparison with conventional and fluid-attenuated inversion recovery, diffusion tensor imaging acquisitions. Imaging 42, — Huang, Z. Longitudinal electrophysiological changes after cervical hemi-contusion spinal cord injury in rats.
Inada, T. Multicenter prospective nonrandomized controlled clinical trial to prove neurotherapeutic effects of granulocyte colony-stimulating factor for acute spinal cord injury: analyses of follow-up cases after at least 1 year. Spine 39, — Ishii, A. Jacobi, A. FGF22 signaling regulates synapse formation during post-injury remodeling of the spinal cord.
EMBO J. James, N. Chondroitinase gene therapy improves upper limb function following cervical contusion injury. Jin, K. Effect of human neural precursor cell transplantation on endogenous neurogenesis after focal cerebral ischemia in the rat.
Johansson, C. Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96, 25— Jones, L. The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury.
Kadoya, K. Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Kaptanoglu, E. Mexiletine treatment-induced inhibition of caspase-3 activation and improvement of behavioral recovery after spinal cord injury. Spine 3, 53— Karimi-Abdolrezaee, S. Delayed transplantation of adult neural precursor cells promotes remyelination and functional neurological recovery after spinal cord injury.
Chondroitinase and growth factors enhance activation and oligodendrocyte differentiation of endogenous neural precursor cells after spinal cord injury. PLoS One 7:e Karus, M. Regulation of oligodendrocyte precursor maintenance by chondroitin sulphate glycosaminoglycans. Glia 64, — Ke, Y. Early response of endogenous adult neural progenitor cells to acute spinal cord injury in mice. Stem Cells 24, — Keirstead, H. Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.
Kerschensteiner, M. In vivo imaging of axonal degeneration and regeneration in the injured spinal cord. Khayrullina, G.
Inhibition of NOX2 reduces locomotor impairment, inflammation, and oxidative stress after spinal cord injury. Kneussel, M. Koffler, J. Biomimetic 3D-printed scaffolds for spinal cord injury repair. Whether the cause is traumatic or nontraumatic, the damage affects the nerve fibers passing through the injured area and can impair part of or all the muscles and nerves below the injury site. A chest thoracic or lower back lumbar injury can affect your torso, legs, bowel and bladder control, and sexual function.
A neck cervical injury affects the same areas in addition to affecting movements of your arms and, possibly, your ability to breathe. Although a spinal cord injury is usually the result of an accident and can happen to anyone, certain factors can predispose you to being at higher risk of having a spinal cord injury, including:.
At first, changes in the way your body functions can be overwhelming. However, your rehabilitation team will help you develop tools to address the changes caused by the spinal cord injury, in addition to recommending equipment and resources to promote quality of life and independence.
Areas often affected include:. Bladder control. Your bladder will continue to store urine from your kidneys. However, your brain might not control your bladder as well because the message carrier the spinal cord has been injured. The changes in bladder control increase your risk of urinary tract infections. The changes may also cause kidney infections and kidney or bladder stones. During rehabilitation, you'll learn ways to help empty your bladder.
Pressure injuries. Below the neurological level of your injury, you might have lost some or all skin sensations. Therefore, your skin can't send a message to your brain when it's injured by certain things such as prolonged pressure. This can make you more susceptible to pressure sores, but changing positions frequently — with help, if needed — can help prevent these sores. You'll learn proper skin care during rehabilitation, which can help you avoid these problems.
Circulatory control. A spinal cord injury can cause circulatory problems ranging from low blood pressure when you rise orthostatic hypotension to swelling of your extremities. These circulation changes can also increase your risk of developing blood clots, such as deep vein thrombosis or a pulmonary embolus. Another problem with circulatory control is a potentially life-threatening rise in blood pressure autonomic dysreflexia.
Your rehabilitation team will teach you how to address these problems if they affect you. Respiratory system. Your injury might make it more difficult to breathe and cough if your abdominal and chest muscles are affected. Your neurological level of injury will determine what kind of breathing problems you have. If you have a cervical and thoracic spinal cord injury, you might have an increased risk of pneumonia or other lung problems.
Medications and therapy can help prevent and treat these problems. Fitness and wellness. Weight loss and muscle atrophy are common soon after a spinal cord injury. Limited mobility can lead to a more sedentary lifestyle, placing you at risk of obesity, cardiovascular disease and diabetes. A dietitian can help you eat a nutritious diet to sustain an adequate weight.
Physical and occupational therapists can help you develop a fitness and exercise program. Drive safely. Car crashes are one of the most common causes of spinal cord injuries. Wear a seat belt every time you're in a moving vehicle. Make sure that your children wear a seat belt or use an age- and weight-appropriate child safety seat.
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