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Spinal cord injury (SCI) may lead to severe motor and sensory dysfunction, causing high mortality and disability rates. Adipose tissue-derived mesenchymal stem/stromal cells (ADSCs), especially hypoxia-pretreated ADSCs, represent an effective therapy for SCI by promoting the secretion of exosomes (Exos). Here, we investigated the therapeutic efficacy of exosomes secreted by ADSCs under hypoxia (HExos) and explored potential target molecules. We utilized nanoparticle tracking analysis, electron microscopy, qRT-PCR, and western blotting to analyze differences between HExos and Exos groups. The expression of long noncoding RNAs (lncRNAs) was examined by high-throughput sequencing. The therapeutic effects of different Exos treatments were compared in vitro and in an SCI model in vivo. The interaction between lncRNAs, microRNAs, and mRNA was examined by luciferase reporter experiments. We employed enzyme-linked immunosorbent assay and immunofluorescence to measure inflammatory factor expression and microglial polarization. The results showed that HExos was more effective than Exos for repairing SCI by suppressing inflammatory factor expression, promoting functional recovery, and shifting microglia from M1 to M2 polarization. High-throughput sequencing showed that LncGm37494 expression was significantly higher in HExos than Exos, and its upregulation promoted microglial M1/M2 polarization by inhibiting miR-130b-3p and promoting PPARγ expression, as shown by luciferase reporter experiments. Exos from lncGm37494 overexpressing ADSCs showed a similar therapeutic effect than HExos. The results indicated that HExos repair SCI by delivering lncGm37494, advising that lncGm3749 functions importantly in microenvironmental regulation and shows possibility for SCI treatments.

To investigate and compare split-hand phenomenon quantified by motor unit number index (MUNIX) between patients with cervical spondylotic amyotrophy (CSA) and those with amyotrophic lateral sclerosis (ALS).MUNIX was performed on abductor pollicis brevis (APB), abductor digiti minimi (ADM) and first dorsal interosseous (FDI) in 46 CSA patients, 39 ALS patients and 41 healthy subjects. Split-hand measurements including split-hand index (SHI=ABP×FDI/ADM), ratio of APB to ADM (AA), ratio of FDI to ADM (FA) were measured by compound muscle action potential (CMAP) and MUNIX.There was a significant difference in both AA and SHI measured by two different methods between ALS and CSA patients (P0.05). Receiver operating characteristic (ROC) curve and logistic regression analysis demonstrated good differential diagnostic accuracy for AA, SHI and their combination between ALS and CSA. A larger area under the curve (AUC) was observed in these measurements calculated by MUNIX than those measured by CMAP (AA: 0.885 vs. 0.700, SHI: 0.865 vs. 0.703, Combination: 0.925 vs. 0.750; P0.05). Sub-group analysis of ROC curves revealed an AUC of 0.893 for AABoth AA and SHI measured by two different methods are useful in distinguishing ALS from CSA, and those quantified by MUNIX may be a better differential diagnostic marker to provide an accurate and noninvasive additional test for distinguishing CSA from ALS, even in their early stages.

Purpose. Bioabsorbable Mg-based implants were previously assessed due to their intrinsic advantages, but Mg-based cage related research is limited. The specific blood supply and stress of the intervertebral environment can affect the function of Mg-based implants. The objective of this study was to investigate the performance of a bioabsorbable Mg-Zn alloy cage in anterior cervical discectomy and fusion (ACDF) and evaluate the control of degradation of the Mg-Zn cage surface modified by microarc oxidation (MAO) technology containing Si under an intervertebral microenvironment. Methods. Twenty-four goats were divided into four groups according to the experimental period and all underwent ACDF at C2-3 and C4-5 with porous Mg-Zn cage covered with a MAO/Si-containing coating in one intervertebral space and with autologous iliac bone in another space. After 3, 6, 12, or 24 weeks after operation, the cervical spine specimens were harvested to evaluate the biocompatibility, fusion status, and degradation conditions using blood analysis, radiology, biomechanical testing, histology, and micro-CT. Results. The Mg-Zn cages showed ideal biocompatibility and biomechanical characterization; however, the fusion state, as evaluated with radiology and histology, was not acceptable. Modified by the MAO/Si-containing coating, the degradation rate of the Mg-Zn cages was controllable but slower than expected. Conclusion. MAO/Si-containing coating Mg-Zn alloy cages demonstrated excessive control of degradation and fusion failure after 24 weeks postoperatively. We conclude that further studies should be designed to improve the using of Mg-based materials at the intervertebral space.

Background Neuroinflammation‐induced secondary injury is an important cause of sustained progression of spinal cord injury. Inflammatory programmed cell death pyroptosis executed by the pore‐forming protein gasdermin D (GSDMD) is an essential step of neuroinflammation. However, it is unclear whether CD73, a widely accepted immunosuppressive molecule, can inhibit pyroptosis via mediating GSDMD. Methods C57BL/6J CD73 deficient mice and wild‐type mice, Lipopolysaccharide (LPS)‐induced primary microglia and BV2 cells were respectively used to illustrate the effect of CD73 on microglia pyroptosis in vivo and in vitro. A combination of molecular and histological methods was performed to assess pyroptosis and explore the mechanism both in vivo and in vitro. Results We have shown molecular evidence for CD73 suppresses the activation of NLRP3 inflammasome complexes to reduce the maturation of GSDMD, leading to decreased pyroptosis in microglia. Further analysis reveals that adenosine‐A2B adenosine receptor‐PI3K‐AKT‐Foxo1 cascade is a possible mechanism of CD73 regulation. Importantly, we determine that CD73 inhibits the expression of GSDMD at the transcriptional level through Foxo1. What's more, we confirm the accumulation of HIF‐1α promotes the overexpression of CD73 after spinal cord injury (SCI), and the increased CD73 in turn upregulates the expression of HIF‐1α, eventually forming a positive feedback regulatory loop. Conclusion Our data reveal a novel function of CD73 on microglia pyroptosis, suggesting a unique therapeutic opportunity for mitigating the disease process in SCI., Inflammatory programmed cell death pyroptosis executed by the pore‐forming protein gasdermin D (GSDMD) is an essential step of neuroinflammation after spinal cord injury. We demonstrated that CD73, a widely accepted immunosuppressive molecule, can inhibit pyroptosis via mediating GSDMD through PI3K/AKT/Foxo1 signaling.

The kinematic characteristics of Modic changes (MCs) in the lumbar spine have rarely been reported; furthermore, the effect of disc degeneration (DD) on segmental motion has not been considered in analyzing the motion characteristics of MCs. Therefore, this study was designed to evaluate the kinematic characteristics of MCs based on different DD grades.894 patients with 4470 lumbar segments were reviewed, and those with MCs were selected for segmental motion evaluation. MC type was defined as 0, I, II, and III, and DD grade was classified into 5 groups from grade A to grade E. Segmental angular and translational motion were calculated from X-ray images in positions of flexion and extension, and the absolute values of the differences were recorded.MCs were observed in 308 segments from 260 patients. No MC was found in DD grade A, and MC III was not observed in DD grade B. MC I was found to significantly increase angular motion in the DD grade E group, and MC II could enlarge translational motion in the DD grade D group (all P0.05); MC III had the lowest segmental motion in both angular and translational motion; There was no statistical difference in angular and translational motion between MC I and II in all DD grade groups (all P0.05).MC III indicates the final stable phase of segmental motion. MC I might increase angular motion, and MC II would increase certain translational motions in the segments that were believed to be stable.

STUDY DESIGN Experimental in vivo and in vitro study of intervertebral disc (IVD) degeneration and the mechanism exploration. OBJECTIVE This report aims to verify the expression of Sirt1 in IVD degeneration of different grades and explore its potential mechanism in human nucleus pulposus cells. SUMMARY OF BACKGROUND DATA Silent mating type information regulator 2 homolog 1 (Sirt1) has draw immense attention because of its influence on a variety of aging-related diseases. The present study is a continuation and complement of our former in vivo study of Sirt1 and its role in puncture-induced rodent disc degeneration model. METHODS Sirt1 protein expression level and histological morphology were evaluated in the discs of different degeneration levels, which is graded according to the Pfirrmann grading scale. Then the mRNA and protein expression levels of type II collagen, MMP-13, ADAMTS-5, p21, p16, cell proliferation, and apoptosis ratio were tested in vitro nucleus pulposus cells that expressed different levels of Sirt1 by reverse transcription polymerase chain reaction, western blot analysis, CCK-8 assay, and flow cytometry analysis. RESULTS Sirt1 protein expression level decreased in the discs of high Pfirrmann grade and the score of histological morphology of human intervertebral disc is consistent with the Pfirrmann grade. Besides, when resveratrol activated Sirt1, nucleus pulposus cells proliferation increased while the cell apoptosis ratio decreased; the expression of type II collagen increased while MMP-13, ADAMTS-5 decreased. It showed the opposite results when the cells were transfected by Sirt1 siRNA. In addition, the expression of both p21 and p16 decreased when Sirt1 was activated. CONCLUSION Sirt1 is a protective mediator in IVD degeneration and the expression of Sirt1 decreases in degenerative disc. Activation of Sirt1 works on suppressing cellular senescence, promoting cell proliferation, and restraining the apoptosis of nucleus pulposus cells. LEVEL OF EVIDENCE N/A.

Purpose. Because Hirayama disease is stereotyped as a self-limited disease in the absence of a definite pathology, we investigated the potential relationship between snake-eyes appearance (SEA) and Hirayama disease to bring a new perspective in the pathological process of Hirayama disease based on relevant radiological and clinical evidence. Methods. A total of 30 cases observed SEA were selected from 293 patients with Hirayama disease to constitute the SEA group, and an equal number of cases were randomly selected from the remaining patients to form the non-SEA group. Cervical magnetic resonance imaging (MRI) was performed and subsequently used to measure the anteroposterior diameter and anterior shifting of the spinal cord. Additionally, clinical data, such as age, sex, duration of symptoms, symptoms, and signs, were collected and analyzed. Results. Of 293 patients, 10.6% appeared with the SEA, which was mainly multisegmental (86.7%), particularly at the C5-6 segment (73.3%), and intense with a well-defined border (70.0%). The SEA group was an older population (p < 0.0001) with a longer duration (p < 0.0001) and a higher incidence of Hoffmann signs and knee hyperreflexia (p < 0.0001, p = 0.0038, respectively). The degree of spinal cord atrophy demonstrated a close association with the SEA, as it was significantly worse in the SEA group and SEA segment (p = 0.0008, p < 0.0001, respectively). The degree of spinal cord atrophy was positively related to both age and duration (p = 0.0095, p = 0.0176, respectively). Conclusions. Confirmed as an irreversible lesion and an indication of poor prognosis, SEA appears during the late stage of Hirayama disease and is closely related to pyramidal signs and spinal cord atrophy.

Background Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states—the classically activated M1 phenotype that confers pro-inflammatory effects or the alternatively activated M2 phenotype that confers anti-inflammatory effects. Ecto-5′-nucleotidase (CD73) is an immunosuppressive molecule intricately involved in adaptive and innate immune responses and is able to dephosphorylate AMP to adenosine. However, it is not known if CD73 is able to modulate the macrophages/microglia transformation between the M1 and M2 phenotypes. Methods We used gene-deficient mice to determine the role of CD73 in macrophages/microglia polarization post-SCI in vivo. We used small interference RNA (siRNA) or pcDNA3.1 to inhibit or overexpress CD73 in BV2 cells to verify anterior discovery in vitro. A combination of molecular and histological methods was used to detect the macrophages/microglia polarization and explore the mechanism both in vivo and in vitro. Results We found that SCI induced the upregulation of CD73 expression. CD73 deficient mice were noted to demonstrate overwhelming immune responses, few anti-inflammatory phenotype macrophages/microglia, and had a poorer locomotor recovery in comparison to wild-type mice that were also inflicted with SCI. In vitro studies found that CD73 suppression inhibited the expression of characteristic microglial anti-inflammatory polarization markers in BV2 cells, while the converse was noted in CD73 overexpression. Subsequent experiments confirmed that CD73 promoted microglia alternative activation by stimulating p38 MAPK. Conclusion We were able to conclude that CD73 imparts neuroprotective effects by mediating macrophages/microglia polarization. These findings allow for better understanding of the modulatory factors involved in triggering the change in macrophages/microglia phenotypes, therefore uncovering additional molecules and pathways that may be targeted in the innovation of novel SCI therapies. Electronic supplementary material The online version of this article (10.1186/s12974-018-1183-8) contains supplementary material, which is available to authorized users.

To determine if the retroperitoneal oblique corridor will be affected by right lateral decubitus position.Forty volunteers were randomly enrolled and MRI scan was performed from L1 to L5 in supine and right lateral decubitus positions, respectively. In images across the center of each disc, O was defined as the center of a disc and A (supine) or A' (right lateral decubitus) was located in left lateral border of the aorta or the iliac artery; B (supine) or B' (right lateral decubitus) was on the anterior medial border of the psoas. The distance of AB and A'B' (Recorded as A-Ps and A-Pr, respectively) at each level was recorded and compared to each other. The relationships between A-Pr, sex, BMI and relative psoas cross-sectional area (PCSA) at each level were also evaluated.A-Pr was significantly smaller than A-Ps at L1/2, L2/3 and L3/4 (All p 0.05); there was no significantly difference of A-Pr between all levels (p = 0.105), but L1/2 seemed to be larger than L3/4, followed by L2/3 and L4/5; A-Pr at each level was not affected by sex (All p 0.05); linear relationships were found between A-Pr, BMI and PCSA at L1/2 and L3/4.ROC at L1/2, L2/3 and L3/4 will significantly decrease from supine to right lateral decubitus position and the reason may be due to the relaxed psoas deformation. Using MRI images in supine position for pre-operatively ROC evaluation is not accurate. Spine surgeon should also be more cautious when OLIF is performed at L4/5 where ROC is the smallest. Patients from Asia and those with strong psoas major at L1/2 and L3/4 are also associated with relatively narrow ROC.