Pediatric and adult spinal cord injuries (SCI) are distinct entities. Children and adolescents with SCI must suffer from lifelong disabilities, which is a heavy burden on patients, their families and the society. There are differences in Chinese and foreign literature reports on the incidence, injury mechanism and prognosis of SCI in children and adolescents. In addition to traumatic injuries such as car accidents and falls, the proportion of sports injuries is increasing. The most common sports injury is the backbend during dance practice. Compared with adults, children and adolescents are considered to have a greater potential for neurological improvement. The pathogenesis and treatment of pediatric SCI remains unclear. The mainstream view is that the mechanism of nerve damage in pediatric SCI include flexion, hyperextension, longitudinal distraction and ischemia. We also discuss the advantages and disadvantages of drugs such as methylprednisolone in the treatment of pediatric SCI and the indications and timing of surgery. In addition, the complications of pediatric SCI are also worthy of attention. New imaging techniques such as diffusion tensor imaging and diffusion tensor tractography may be used for diagnosis and assessment of prognosis. This article reviews the epidemiology, pathogenesis, imaging, clinical characteristics, treatment and complications of SCI in children and adolescents. Although current treatment cannot completely restore neurological function, patient quality of life can be enhanced. Continued developments and advances in the research of SCI may eventually provide a cure for children and adolescents with this kind of injury.
Adult ; Child ; Humans ; Adolescent ; Diffusion Tensor Imaging/methods* ; Quality of Life ; Spinal Cord Injuries/therapy* ; Prognosis ; Athletic Injuries ; Spinal Cord/pathology*

Spinal cord injury (SCI) disrupts the structural and functional connectivity between the higher center and the spinal cord, resulting in severe motor, sensory, and autonomic dysfunction with a variety of complications. The pathophysiology of SCI is complicated and multifaceted, and thus individual treatments acting on a specific aspect or process are inadequate to elicit neuronal regeneration and functional recovery after SCI. Combinatory strategies targeting multiple aspects of SCI pathology have achieved greater beneficial effects than individual therapy alone. Although many problems and challenges remain, the encouraging outcomes that have been achieved in preclinical models offer a promising foothold for the development of novel clinical strategies to treat SCI. In this review, we characterize the mechanisms underlying axon regeneration of adult neurons and summarize recent advances in facilitating functional recovery following SCI at both the acute and chronic stages. In addition, we analyze the current status, remaining problems, and realistic challenges towards clinical translation. Finally, we consider the future of SCI treatment and provide insights into how to narrow the translational gap that currently exists between preclinical studies and clinical practice. Going forward, clinical trials should emphasize multidisciplinary conversation and cooperation to identify optimal combinatorial approaches to maximize therapeutic benefit in humans with SCI.
Humans ; Axons/pathology* ; Nerve Regeneration/physiology* ; Spinal Cord Injuries/therapy* ; Neurons/pathology* ; Recovery of Function

Spinal cord injury (SCI), which is much in the public eye, is still a refractory disease compromising the well-being of both patients and society. In spite of there being many methods dealing with the lesion, there is still a deficiency in comprehensive strategies covering all facets of this damage. Further, we should also mention the structure called the corticospinal tract (CST) which plays a crucial role in the motor responses of organisms, and it will be the focal point of our attention. In this review, we discuss a variety of strategies targeting different dimensions following SCI and some treatments that are especially efficacious to the CST are emphasized. Over recent decades, researchers have developed many effective tactics involving five approaches: (1) tackle more extensive regions; (2) provide a regenerative microenvironment; (3) provide a glial microenvironment; (4) transplantation; and (5) other auxiliary methods, for instance, rehabilitation training and electrical stimulation. We review the basic knowledge on this disease and correlative treatments. In addition, some well-formulated perspectives and hypotheses have been delineated. We emphasize that such a multifaceted problem needs combinatorial approaches, and we analyze some discrepancies in past studies. Finally, for the future, we present numerous brand-new latent tactics which have great promise for curbing SCI.
Animals ; Astrocytes/cytology* ; Axons/physiology* ; Cell Transplantation ; Disease Models, Animal ; Electric Stimulation ; Humans ; Microglia/cytology* ; Motor Neurons/cytology* ; Nerve Regeneration ; Neuroglia/cytology* ; Neuronal Plasticity ; Neurons/cytology* ; Oligodendroglia/cytology* ; Pyramidal Tracts/pathology* ; Recovery of Function ; Regenerative Medicine/methods* ; Spinal Cord Injuries/therapy*

Evidence suggested that glycogen synthase kinase-3β (GSK-3β) is involved in Nogo-66 inhibiting axonal regeneration in vitro, but its effect in vivo was poorly understood. We showed that stereotactic injection of shRNA GSK-3β-adeno associated virus (GSK-3β-AAV) diminished syringomyelia and promoted axonal regeneration after spinal cord injury (SCI), using stereotactic injection of shRNA GSK-3β-AAV (tested with Western blotting and RT-PCR) into the sensorimotor cortex of rats with SCI and by the detection of biotin dextran amine (BDA)-labeled axonal regeneration. We also determined the right position to inject into the sensorimotor cortex. Our findings consolidate the hypothesis that downregulation of GSK-3β promotes axonal regeneration after SCI.
Animals ; Axons ; drug effects ; metabolism ; Dependovirus ; genetics ; Glycogen Synthase Kinase 3 beta ; genetics ; metabolism ; Humans ; Nerve Regeneration ; genetics ; RNA, Small Interfering ; administration & dosage ; genetics ; Rats ; Sensorimotor Cortex ; drug effects ; pathology ; Spinal Cord Injuries ; genetics ; pathology ; therapy ; Syringomyelia ; genetics ; pathology ; therapy

OBJECTIVETo explore the effect of electro-acupuncture to improve the bladder function after acute spinal cord injury in rats and its possible mechanism.

METHODSSixty healthy adult male SD rats of SPF grade, with body weight of 220 to 250 g, one week after feeding adaptation, were randomly divided into sham operation group, model group, electro-acupuncture group, electro-acupuncture control group with 15 rats in each group. Sham operation group underwent no stimulation, and the moderate damage model of spinal cord injury were made in other three groups according to modified Allens method. The model group were not treated, electro-acupuncture group were treated with electro-acupuncture on Zhibianxue and Shuidaoxue, and electro-acupuncture control group were treated with electro-acupuncture on 0.5 inch next to Zhibianxue and Shuidaoxue. The frequency of 2/100 Hz, current of 1 mA, stimulation time of 15 min, once a day, left and right alternately stimulate every time, for a total of 7 times. The changes of residual urine volume and urine output in rats at the 1st and the 7th days after operation were observed. And 7 d later, the rats were sacrificed and the injured spinal cord were taken out to observe the apoptosis, and to detect the changes of Bcl-2, Bax, Bad content.

RESULTSAfter modeling,the rats of three groups showed different bladder dysfunction. In electro-acupuncture group and electro-acupuncture control group, the residual urine volume of the 7th day after operation was significant lower than the 1st day after operation (P < 0.001), and there was statistically significant difference on the 7th day after operation between two groups (P < 0.001). Compared with model group, the urine output of electro-acupuncture group and electro-acupuncture control group was significantly increased on the 7th day after operation, and there was sig- nificant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.001). Electro-acupuncture can inhibit apoptosis of spinal cord neurons by TUNEL detection. Postoperative at 7 d, the rate of nerve cell apoptosis in electro -acupuncture group and electro-acupuncture control group was significant increased than model group (P < 0.01, P < 0.05), and there was significant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.005). Compared with model group, the positive expression rate of Bax, Bad decreased (P < 0.01, P < 0.05), and Bcl-2 increased (P < 0.01) in electro-acupuncture group and electro-acupuncture control group,there was significant difference between electro-acupuncture group and electro-acupuncture control group (P < 0.01).

CONCLUSIONElectro-acupuncture can obviously promote the repair of acute spinal cord injury,its mechanism may be through increasing Bcl-2, inhibiting the expression of Bax, Bad, which inhibits the apoptosis of spinal cord neurons.

Animals ; Apoptosis ; Electroacupuncture ; Immunohistochemistry ; In Situ Nick-End Labeling ; Male ; Neurons ; cytology ; physiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; pathology ; physiopathology ; therapy ; Urinary Bladder ; physiopathology

OBJECTIVETo observe the change of behavior, pathological change of the spinal cord,and expression of brain-derived neurotrophic factor (BDNF) and brain-derived neurotrophic factor (NGF) on rats with spinal cord injury in order to explore the optimal time of BMSCs transplantation.

METHODSEighty health SD rats were randomly divided into 8 groups (group A,B,C,D,E,F,G,H), 10 rats in each group. According to the modified Allen method,the rat model of spinal cord injury was built. Group A as non-injured group only exposed the spinal cord but not result in blast injury. BMSCs of vitro culture were respectively infunded the region of spinal cord injury in group C, D, E, F, G, H (as transplantation groups) at the 0 h, 6 h, 24 h,3 d,5 d,7 d after model made. Group B as single model group was infunded the equal cell culture fluid. BBB score was used to evaluate the function of spinal cord at the 1st,2nd and 4th weeks after injury. The morphological changes of the tissue of spinal cord injury were observed by HE stain and the expression of BDNF and NGF were detected by Elisa method at the 4th weeks after BMSCs transplantation.

RESULTSIn non-injured group,BBB score was highest than that of other 7 groups at the 1st, 2nd and 4th weeks after injury (P<0.01). There was no significant difference in BBB score between single model group and transplantation groups at the 1st week after BMSCs transplantation (P>0.05). BBB score in transplantation groups were higher than that of single model group at the 2nd and 4th weeks after BMSCs transplantation (P<0.05). At the 2nd week after injury, BBB score from high to low was group F,E,G,D,H,C,but there was no significant difference among the groups (P>0.05). At the 4th week after injury,there was significant differences in BBB score between group F and other transplantation groups (group C,D,E,G,H)(P0.05). The levels of BDNF and NGF in group F was highest at the 4th week after BMSCs transplantation (P<0.05). In non-injured group,HE staining showed the struction of spinal cord was clear and complete,no neutrophil was found. But in other 7 groups,HE staining showed obviously oedema at local tissue,juncture of gray and white matter was undefined,and different gliocyte proliferation and inflammatory cell infiltrate cound be found.

CONCLUSIONAllogeneic BMSCs transplantation is effective to stimulate the recovery of spinal cord function in rats with spinal cord injury,and the optimal time of BMSCs transplantation maybe at the 3 d after injury.

Animals ; Behavior, Animal ; Brain-Derived Neurotrophic Factor ; genetics ; Female ; Male ; Mesenchymal Stem Cell Transplantation ; Nerve Growth Factor ; genetics ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries ; metabolism ; pathology ; therapy ; Transplantation, Homologous

BACKGROUNDAfter injury, axonal regeneration of the adult central nervous system (CNS) is inhibited by myelin-derived growth-suppressing proteins. These axonal growth inhibitory proteins are mediated via activation of Rho, a small GTP-binding protein. The activated form of Rho, which is bound to GTP, is the direct activator of Rho kinase (ROCK) through serial downstream effector proteins to inhibit axonal regeneration. The objective of this study was to observe the therapeutic effect of inactivation of the Rho-ROCK signaling pathway to promote neurologic recovery after spinal cord injuries in rats.

METHODSOne hundred and twenty adult female Sprague-Dawley rats were randomly divided into three groups. Laminectomies alone were conducted in 40 rats in the sham group. Laminectomies and spinal cord transections were performed in 40 rats in the control group (treated with normal saline administered intraperitoneally). Laminectomies and spinal cord transections were performed in 40 rats in the fasudil-treated group (treated with fasudil administered intraperitoneally). Neurologic recovery was evaluated before surgery and 3 days, and 1, 2, 3, and 4 weeks after surgery using the Basso-Beattie-Bresnahan (BBB) scale of hind limb movement. At the same time, the expression of RhoA mRNA was determined with RT-PCR. Histopathologic examinations and immunofluorescence staining of NF were performed 1 month after surgery.

RESULTSCompared with the control group, the BBB scores of the fasudil-treated group were significantly increased and the expression of RhoA mRNA was significantly decreased. In the fasudil-treated group, a large number of NF-positive regenerating fibers was observed; some fibers crossed the slit of the lesion.

CONCLUSIONInactivation of the Rho-ROCK signaling pathway promotes CNS axonal regeneration and neurologic recovery after spinal cord injuries in rats.

Animals ; Female ; Fluorescent Antibody Technique ; Nerve Regeneration ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; physiology ; Spinal Cord Injuries ; pathology ; physiopathology ; psychology ; therapy ; rho-Associated Kinases ; antagonists & inhibitors ; physiology ; rhoA GTP-Binding Protein ; antagonists & inhibitors ; physiology

Spinal cord injury (SCI) causes not only loss of sensory and motor function below the level of injury but also chronic pain, which is difficult and challenging of the treatment. Repetitive transcranial magnetic stimulation (rTMS) to the motor cortex, of non-invasive therapeutic methods, has the motor and sensory consequences and modulates pain in SCI-patients. In the present study, we studied the effectiveness of rTMS and the relationship between the modulation of pain and the changes of neuroglial expression in the spinal cord using a rat SCI-induced pain model. Elevated expressions of Iba1 and GFAP, specific microglial and astrocyte markers, was respectively observed in dorsal and ventral horns at the L4 and L5 levels in SCI rats. But in SCI rats treated with 25 Hz rTMS for 8 weeks, these expressions were significantly reduced by about 30%. Our finding suggests that this attenuation of activation by rTMS is related to pain modulation after SCI. Therefore, rTMS might provide an alternative means of attenuating neuropathic pain below the level of SCI.
Animals ; Astrocytes/*cytology ; Calcium-Binding Proteins/metabolism ; Disease Models, Animal ; Immunohistochemistry ; Male ; Microfilament Proteins/metabolism ; Microglia/*cytology ; Nerve Tissue Proteins/metabolism ; Neuralgia/etiology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries/complications/pathology/*therapy ; *Transcranial Magnetic Stimulation

Transcatheter arterial chemoembolization (TACE) has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.
Antiviral Agents/therapeutic use ; Bone Neoplasms/radiography/secondary ; Carcinoma, Hepatocellular/diagnosis/pathology/*therapy ; Catheter Ablation ; Chemoembolization, Therapeutic/*adverse effects ; Hepatitis B/complications/drug therapy ; Humans ; Liver Cirrhosis/etiology ; Liver Neoplasms/diagnosis/pathology/*therapy ; Male ; Middle Aged ; Positron-Emission Tomography ; Soft Tissue Neoplasms/secondary ; Spinal Cord Injuries/*etiology ; Tomography, X-Ray Computed

Spinal cord injury (SCI) is frequently companied by necrosis and apoptosis of oligodendrocytes (OLs), which contributes to demyelination of myelinated nerve fibers and their electrophysiological defects. This pathological demyelination often results in sensory or motor deficits. Here, we first focus on the microenvironment changes after SCI that cause OLs' death, then discuss the major mechanism of endogenous oligodendrocytogenesis and axonal remyelination, and finally summarize current therapies targeting OLs protection and replacement.
Animals ; Apoptosis ; physiology ; Cell Death ; physiology ; Humans ; Necrosis ; pathology ; Nerve Fibers, Myelinated ; pathology ; Nerve Regeneration ; physiology ; Oligodendroglia ; pathology ; Spinal Cord ; physiopathology ; Spinal Cord Injuries ; pathology ; physiopathology ; therapy