1.Progress on the role of autophagy in spinal cord injury.
Kai-liang ZHOU ; Xiao-lei ZHANG ; Kai WU ; Yong-li WANG ; Hua-zi XU
China Journal of Orthopaedics and Traumatology 2015;28(8):695-698
In recent years, the study of autophagy in spinal cord injury (SCI) gradually becomes the hot spot. However, the function of autophagy in the injured spinal cord is still controversial. In order to further understand the role of autophagy after SCI, we summarized the activation of autophagy, autophagic cell death, the relationship between autophagy and apoptosis, the function of autophagy in promoting the molecular metabolism and the role of autophagy after spinal cord injury. We concluded that the role of autophagy after SCI is a double-edged sword. Upregulating the level of autophagy appropriately can promote damaged proteins metabolism and inhibit apoptosis. However, excessive activation of antophagy may induce autophagic cell dealth. So we consider that the proper regulation of autophagy will be a new target in the treatment of SCI.
Animals
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Apoptosis
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Autophagy
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physiology
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Humans
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Spinal Cord Injuries
;
etiology
;
pathology
3.Spatiotemporal Dynamics of the Molecular Expression Pattern and Intercellular Interactions in the Glial Scar Response to Spinal Cord Injury.
Leilei GONG ; Yun GU ; Xiaoxiao HAN ; Chengcheng LUAN ; Chang LIU ; Xinghui WANG ; Yufeng SUN ; Mengru ZHENG ; Mengya FANG ; Shuhai YANG ; Lai XU ; Hualin SUN ; Bin YU ; Xiaosong GU ; Songlin ZHOU
Neuroscience Bulletin 2023;39(2):213-244
Nerve regeneration in adult mammalian spinal cord is poor because of the lack of intrinsic regeneration of neurons and extrinsic factors - the glial scar is triggered by injury and inhibits or promotes regeneration. Recent technological advances in spatial transcriptomics (ST) provide a unique opportunity to decipher most genes systematically throughout scar formation, which remains poorly understood. Here, we first constructed the tissue-wide gene expression patterns of mouse spinal cords over the course of scar formation using ST after spinal cord injury from 32 samples. Locally, we profiled gene expression gradients from the leading edge to the core of the scar areas to further understand the scar microenvironment, such as neurotransmitter disorders, activation of the pro-inflammatory response, neurotoxic saturated lipids, angiogenesis, obstructed axon extension, and extracellular structure re-organization. In addition, we described 21 cell transcriptional states during scar formation and delineated the origins, functional diversity, and possible trajectories of subpopulations of fibroblasts, glia, and immune cells. Specifically, we found some regulators in special cell types, such as Thbs1 and Col1a2 in macrophages, CD36 and Postn in fibroblasts, Plxnb2 and Nxpe3 in microglia, Clu in astrocytes, and CD74 in oligodendrocytes. Furthermore, salvianolic acid B, a blood-brain barrier permeation and CD36 inhibitor, was administered after surgery and found to remedy fibrosis. Subsequently, we described the extent of the scar boundary and profiled the bidirectional ligand-receptor interactions at the neighboring cluster boundary, contributing to maintain scar architecture during gliosis and fibrosis, and found that GPR37L1_PSAP, and GPR37_PSAP were the most significant gene-pairs among microglia, fibroblasts, and astrocytes. Last, we quantified the fraction of scar-resident cells and proposed four possible phases of scar formation: macrophage infiltration, proliferation and differentiation of scar-resident cells, scar emergence, and scar stationary. Together, these profiles delineated the spatial heterogeneity of the scar, confirmed the previous concepts about scar architecture, provided some new clues for scar formation, and served as a valuable resource for the treatment of central nervous system injury.
Mice
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Animals
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Gliosis/pathology*
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Cicatrix/pathology*
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Spinal Cord Injuries
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Astrocytes/metabolism*
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Spinal Cord/pathology*
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Fibrosis
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Mammals
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Receptors, G-Protein-Coupled
4.Clinical characteristics and treatment of spinal cord injury in children and adolescents.
Jin-Zuo WANG ; Ming YANG ; Meng MENG ; Zhong-Hai LI
Chinese Journal of Traumatology 2023;26(1):8-13
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
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Child
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Humans
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Adolescent
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Diffusion Tensor Imaging/methods*
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Quality of Life
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Spinal Cord Injuries/therapy*
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Prognosis
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Athletic Injuries
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Spinal Cord/pathology*
5.Early neurosurgical intervention of spinal cord contusion: an analysis of 30 cases.
Hui ZHU ; Ya-ping FENG ; Wise YOUNG ; Si-wei YOU ; Xue-feng SHEN ; Yan-sheng LIU ; Gong JU
Chinese Medical Journal 2008;121(24):2473-2478
BACKGROUNDThe incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study.
METHODSA total of 30 patients with "complete" spinal cord injury or classified as American Spinal Injury Association (ASIA)-A were studied. Orthopedic treatment of the injured vertebra (e), internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis.
RESULTSAll the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint (12 cases, 40%). Thirteen patients (43%) were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4 - 14 days after injury.
CONCLUSIONSEarly neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.
Adolescent ; Adult ; Humans ; Male ; Middle Aged ; Spinal Cord ; pathology ; surgery ; Spinal Cord Injuries ; pathology ; surgery ; Treatment Outcome ; Young Adult
6.Protective effect of velvet antler polypeptide (VAP) on rats with the spinal cord injury.
Zhen-hua LI ; Xiang-yang LENG ; Zhong-li GAO
China Journal of Orthopaedics and Traumatology 2008;21(4):285-286
OBJECTIVETo investigate the protective effect of antler polypeptide on the rats with spinal cord injury (SCI).
METHODSThe model rats were treated with different doses of antler polypeptide, and its effect on motor function, ethology and pathological changes of spinal cord of the rats observed.
RESULTSSeven days after treatment with different doses of antler polypeptide, rat's motor activity was recovered in some extent. Significant difference (P < 0.001)was found between the antler polypeptide treatment group and operation group. The effect could be enhanced by increase of the doses. We observerd the effect on the pathological change of spinal cord in rat, and found the tissue edema and inflammatory infiltration were relieved after treatment with different doses of antler polypeptide, especially in the dose of 15 mg antler polypeptide.
CONCLUSIONAntler polypeptide can promote the motor function recovery in SCI rats, and its action is dose-dependent.
Animals ; Antlers ; chemistry ; Male ; Peptides ; therapeutic use ; Rats ; Rats, Wistar ; Spinal Cord ; pathology ; Spinal Cord Injuries ; drug therapy ; pathology
7.Urethral Pressure Measurement as a Tool for the Urodynamic Diagnosis of Detrusor Sphincter Dyssynergia.
Lauren E CORONA ; Anne P CAMERON ; J Quentin CLEMENS ; Yongmei QIN ; John T STOFFEL
International Neurourology Journal 2018;22(4):268-274
PURPOSE: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. METHODS: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. RESULTS: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm H₂O urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm H₂O during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10–500 seconds) and mean urethral pressure amplitude was 73 cm H₂O (range, 1–256 cm H₂O). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. CONCLUSIONS: Urethral pressure amplitude of >20 cm H2O during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.
Ataxia*
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Diagnosis*
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Electromyography
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Humans
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Male
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Multiple Sclerosis
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Pathology
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Phenotype
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Physiology
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Retrospective Studies
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Spinal Cord
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Spinal Cord Injuries
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Urinary Bladder
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Urodynamics*
8.Spinal Cord Tumors: An Analysis of 654 Cases(1973-1999).
Woo Jin CHOE ; Chun Kee CHUNG ; Byung Kyu CHO ; Hyun Jib KIM
Journal of Korean Neurosurgical Society 2001;30(8):1004-1012
OBJECTIVE: The spinal cord tumors(including vertebral tumors) are increasingly diagnosed and operated due to development of refined diagnostic and therapeutic tools. It is necessary to re-evaluate clinical features and surgical results of spinal cord tumors with increasing cases and developing treatment modalities. The authors reviewed the spinal cord tumor cases to evaluate their clinical characteristics. MATERIALS AND METHODS: The retrospective review of 654 cases of spinal cord tumors between 1973 and 1999 was done. The clinical features, pathological analysis and surgical results were analyzed and compared to the literature. The results of the study are analyzed with a more detailed consideration of each of major pathologies: neurogenic tumors, meningeal tumors, neuroepithelial tumors, and metastatic tumors. RESULTS AND CONCLUSION: The spinal cord tumor was most common in the 5th decade of age(145 cases, 22.1%) and 78 cases(11.9%) were found in children under 15 years of age. The ratio of male to female was 1.2:1. The pathologic diagnosis was neurogenic tumor in 266 cases(40.7%), neuroepithelial tumor in 131(20.0%), metastatic tumor in 118(18.0%), and meningeal tumor in 94(14.4%) in the order of frequency. The tumor was located most frequently in the thoracic area(36.5%) and in the intradural extramedullary space(38.1%). The most common initial presentation was pain(40.1%) and the mean duration for presentation to operation was 14.8 months. The total or gross total removal was possible in 404 cases(61.7%) and the surgical result on the postoperative one month was recovery or improvement in 424 cases(64.8%), stationary in 188(28.7%), progression in 42(6.4%). As a surgical complication, there was a spinal deformity(12 cases), wound infection(5 cases), aspiration pneumonia(5 cases) etc. Neurogenic tumors and menigiomas showed good surgical results, whereas neuroepithelial tumors(except ependymoma) and metastatic tumors showed relatively poor prognosis.
Child
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Diagnosis
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Female
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Humans
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Male
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Meningeal Neoplasms
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Neoplasms, Neuroepithelial
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Pathology
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Prognosis
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Retrospective Studies
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Spinal Cord Neoplasms*
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Spinal Cord*
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Wounds and Injuries
10.Recent progress and challenges in the treatment of spinal cord injury.
Ting TIAN ; Sensen ZHANG ; Maojun YANG
Protein & Cell 2023;14(9):635-652
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
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Axons/pathology*
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Nerve Regeneration/physiology*
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Spinal Cord Injuries/therapy*
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Neurons/pathology*
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Recovery of Function