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Functional and pathological recovery after spinal cord injury (SCI) is often incomplete due to the limited regenerative capacity of the central nervous system (CNS), which is further impaired by several mechanisms that sustain tissue damage. Among these, the chronic activation of immune cells can cause a persistent state of local CNS inflammation and damage. However, the mechanisms that sustain this persistent maladaptive immune response in SCI have not been fully clarified yet. In this study, we integrated histological analyses with proteomic, lipidomic, transcriptomic, and epitranscriptomic approaches to study the pathological and molecular alterations that develop in a mouse model of cervical spinal cord hemicontusion. We found significant pathological alterations of the lesion rim with myelin damage and axonal loss that persisted throughout the late chronic phase of SCI. This was coupled by a progressive lipid accumulation in myeloid cells, including resident microglia and infiltrating monocyte-derived macrophages. At tissue level, we found significant changes of proteins indicative of glycolytic, tricarboxylic acid cycle (TCA), and fatty acid metabolic pathways with an accumulation of triacylglycerides with C16:0 fatty acyl chains in chronic SCI. Following transcriptomic, proteomic, and epitranscriptomic studies identified an increase of cholesterol and m 6 A methylation in lipid-droplet-accumulating myeloid cells as a core feature of chronic SCI. By characterizing the multiple metabolic pathways altered in SCI, our work highlights a key role of lipid metabolism in the chronic response of the immune and central nervous system to damage., Competing Interests: Declaration of competing interest The authors declare no competing financial and/or non-financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Macrophages and microglia play important roles in chronic neuroinflammation following spinal cord injury (SCI). Although macrophages and microglia have similar functions, their phagocytic and homeostatic abilities differ. It is difficult to distinguish between these two populations in vivo , but single-cell analysis can improve our understanding of their identity and heterogeneity. We conducted bioinformatics analysis of the single-cell RNA sequencing dataset GSE159638, identifying apolipoprotein E (APOE) as a hub gene in both macrophages and microglia in the subacute and chronic phases of SCI. We then validated these transcriptomic changes in a mouse model of cervical spinal cord hemi-contusion and observed myelin uptake, lipid droplets, and lysosome accumulation in macrophages and microglia following SCI. Finally, we observed that knocking out APOE aggravated neurological dysfunction, increased neuroinflammation, and exacerbated the loss of white matter. Targeting APOE and the related cholesterol efflux represents a promising strategy for reducing neuroinflammation and promoting recovery following SCI., Competing Interests: 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., (Copyright © 2022 Yao, Chen, Yu, Huang, Hamel, Zeng, Huang, Tu, Liu, Lu, Zhou, Pluchino, Zhu and Chen.)

Neuroinflammation is recognized as a hallmark of spinal cord injury (SCI). Although neuroinflammation is an important pathogenic factor that leads to secondary injuries after SCI, neuroprotective anti-inflammatory treatments remain ineffective in the management of SCI. Moreover, the molecular signatures involved in the pathophysiological changes that occur during the course of SCI remain ambiguous. The current study investigated the proteins and pathways involved in C5 spinal cord hemi-contusion injury using a rat model by means of 4-D label-free proteomic analysis. Furthermore, two Gene Expression Omnibus (GEO) transcriptomic datasets, Western blot assays, and immunofluorescent staining were used to validate the expression levels and localization of dysregulated proteins. The present study observed that the rat models of SCI were associated with the enrichment of proteins related to the complement and coagulation cascades, cholesterol metabolism, and lysosome pathway throughout the acute and subacute phases of injury. Intriguingly, the current study also observed that 75 genes were significantly altered in both the GEO datasets, including ANXA1, C1QC, CTSZ, GM2A, GPNMB, and PYCARD. Further temporal clustering analysis revealed that the continuously upregulated protein cluster was associated with immune response, lipid regulation, lysosome pathway, and myeloid cells. Additionally, five proteins were further validated by means of Western blot assays and the immunofluorescent staining showed that these proteins coexisted with the F4/80+ reactive microglia and infiltrating macrophages. In conclusion, the proteomic data pertaining to the current study indicate the notable proteins and pathways that may be novel therapeutic targets for the treatment of SCI., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Context: Considerable controversy exists over surgical procedures for ossification of the posterior longitudinal ligament (OPLL). Objective: The purpose of the meta-analysis was to compare the clinical outcome of anterior decompression and fusion (ADF) with laminoplasty (LAMP) in treatment of cervical myelopathy due to OPLL. Methods: PubMed, EMBASE and the Cochrane Register of Controlled Trials database were searched to identify potential clinical studies compared ADF with LAMP for cervical myelopathy owing to OPLL. We also manually searched the reference lists of articles and reviews for possible relevant studies. Thirteen studies with 1120 patients were included in our analysis. Subgroup analyses were performed by the canal occupying ratio of OPLL. Results: Overall, the mean preoperative Japanese Orthopaedic Association (JOA) score was similar between two groups. Compared with LAMP group, ADF group was higher at the mean postoperative JOA scores and mean recovery rate, reoperation rate, and longer at mean operation time. There was not significantly different in mean blood loss and complication rate between two groups. In subgroup analysis, ADF had a higher mean postoperative JOA score and recovery rate than LAMP in cases of OPLL with occupying ratios ≥ 50%, while those difference were not found in cases of OPLL with occupying ratios < 50%. Conclusion: ADF achieves better neurological improvement compared with LAMP in treatment of cervical myelopathy due to OPLL, especially in cases of OPLL with occupying ratios ≥ 50%. Complication rate is similar between two groups, but ADF can increase the risk of reoperation.

Mesenchymal stem cells derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, mouse adipose-derived stem cells (ADSCs) were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD29, CD44, CD71, CD73, CD90, CD105, CD166, Nestin, GFAP and MAP-2 were detected by immunofluorescence assays. The ADSCs were cultured in cocktail factors (including ATRA, GGF-2, bFGF, PDGF and forskolin) for neurogenic differentiation. The neurogenic cells markers, Nestin, GFAP and MAP-2 were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Neurogenic cells from ADSCs were autologous transplanted into the mouse of spinal cord injury for observation neurogenic cells colonization in spinal cord. The result demonstrated that the mouse ADSCs were positive for the CD13, CD29, CD44, CD71, CD73, CD90, CD105 and CD166 but negative for neurogenic cell markers, MAP-2, GFAP and Nestin. After neurogenic differentiation, the neurogenic cells were positive for neurogenic cell special markers, gene expression level showed a time-lapse increase, and the cells were successful colonized into spinal cord. In conclusion, our research shows that a population of neuronal cells can be specifically generated from ADSCs and that induced cells may allow for participation in tissue-repair.

In this research, mouse BMMSCs were isolated from bone marrow, induced to differentiate into neurogenic cells in vitro, and transplanted into the injured spinal cord after over-expression of miR-124. The results showed that the BMMSCs could induce the differentiation to neurogenic cells under the special condition medium, but when the miR-124 was over-expressed, the differentiation efficiency of neurogenic cells from BMMSCs could be promoted. This reason was demonstrated that polypyrimidine tract-binding protein 1 (PTBP1) showed a repressor for polypyrimidine tract-binding protein 2 (PTBP2) during neuronal differentiation, miR-124 reduces PTBP1 levels, leading to the accumulation of correctly spliced PTBP2 mRNA and a dramatic increase in PTBP2 protein. miR-124 promoted neurogenic cells from BMMSCs were successful colonized into injured spinal cord for participation in tissue-repair. In conclusion, our research shows that the miR-124 promoted the differentiation of neuronal cells from BMMSCs, and this mechanism was miR-124 reduced the expression of PTBP1, increased the expression of PTBP2., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To investigate how to select an appropriate surgical approach in the management of fracture and dislocation of lower cervical spine combined spinal cord injury., Methods: The clinical data of 54 patients of lower cervical spine fracture and dislocation were retrospectively analyzed. There were 29 cases with vertebral body compressive fracture and dislocation, 7 cases with vertebral body bursting fracture and dislocation, 3 cases with unilateral facet dislocation, 15 cases with bilateral facet dislocation. All cases were associated with spinal cord injury. According to American Spinal Injury Association (ASIA) grades, 21 cases were in A grade, 5 cases in B grade, 22 cases in C grade and 6 cases in D grade. All patients had surgical reduction, decompression, stabilization and fusion, 43 cases in anterior approach and 11 cases in posterior approach., Results: All patients were followed up in 12 to 36 months, the mean follow-up time was 18 months. There were no great vessels, trachea, esophagus or spinal cord iatrogenic injury. There were no pull-out and breakage of screws or plates. Fusion was achieved in all patients at an average of 12 weeks postoperatively. There were no pseudarthrosis or bone nonunion. Of all the patients, 96.3% were acquired completely reduction and the normal intervertebral height and lordosis were maintained. Patients with complete spinal cord had no neurologic recovery, but they felt relief from upper limb pain or numb. Incomplete spinal cord lesions improved on average 1-2 Frankel grade after surgery., Conclusions: For lower cervical spine fracture and dislocation, an ideal anatomy reduction can be obtained with either anterior or posterior approach surgery. It is important to select a suitable surgical approach according to different types of cervical fracture and dislocation.

Objective: To evaluate the therapeutic effect of several internal fixation methods in the surgical treatment of thoracolumbar spine and spinal cord injury (SSI-TL)., Methods: In the 166 SSI-TL cases included in this retrospective analysis, 37 had vertebral body burst fracture, 109 had vertebral body compression fracture (with compression to a degree over 50%),14 had vertebral body fracture and dislocation and 6 had multilevel vertebral fractures or jumping fracture. In view of the spinal cord injury 59 belonged to Frankel grade A, 46 grade B, 42 grade C and 19 grade D. Posterior decompression, reduction and internal fixation were performed in 122 patients and the other 44 underwent anterior decompression, reduction and ilium bone grafting., Results: Follow-up study for 3 to 18 month was conducted in 123 cases, in which RF screws cracking occurred in 4 cases, Harrington upper hook dislocation in 5 cases and Harrington rod cracking in 6, while the rest cases were free of theses incidents. In terms of the function recovery of the spinal cord, 88 cases showed improvement of the spinal cord and cauda equina of 1 to 3 Frankel grades, leaving only 35 lingering in grade A., Conclusion: Decompression should be performed at early stages of SSI-TL, and employment of various internal fixation instrument helps maintain and enhance spinal stability, preventing secondary lesion of the spinal cord and promoting the function recovery of the injured spinal cord.

Bladder dysfunction is a common complication after chronic spinal cord injury (SCI). Patients may experience renal function loss, urinary tract infection (UTI), urolithiasis, bladder cancer, and even life-threatening events such as severe sepsis or renal failure. Suitable patient care may prevent UTI and urinary incontinence, decrease medication use, and preserve renal function. As the primary goal is to preserve renal function, management should be focused on facilitating bladder drainage, the avoidance of UTI, and the maintenance of a low intravesical pressure for continence and complete bladder emptying. Currently, several bladder management options are available to SCI patients: (1) reflex voiding; (2) clean intermittent catheterization; (3) indwelling catheterization. The target organ may be the bladder or the bladder outlet. The purposes of intervention include the following: (1) increasing bladder capacity and/or decreasing intravesical pressure; (2) increasing bladder outlet resistance; (3) decreasing bladder outlet resistance; (4) producing detrusor contractility; (5) urinary diversion. Different bladder management methods and interventions may have different results depending on the patient's lower urinary tract dysfunction. This review aims to report the current management options for long-term bladder dysfunction in chronic SCI patients. Furthermore, we summarize the most suitable care plans for improving the clinical outcome of SCI patients. [ABSTRACT FROM AUTHOR]