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Background: Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Methods: Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. Results: Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. Conclusion: This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified.Methods: Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro.Results: Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis.Conclusion: This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to assess the nerve function deficient recovery in surgically treated patients with cervical trauma with spinal cord injury (SCI) in chronic stage and figure out prognostic predictors of improvement in impairment and function. Methods: We reviewed the clinical and radiological data of 143 cervical SCI patients in chronic stage and divided into non-operative group (n = 61) and operative group (n = 82). The severity of neurological involvement was assessed using the ASIA motor score (AMS) and Functional Independence Measure Motor Score (FIM MS). The health-related quality of life was measured using the SF-36 questionnaire. Correspondence between the clinical and radiological findings and the neurological outcome was investigated. Results: At 2-year follow-up, surgery resulted in greater improvement in AMS and FIM MS than non-operative group. Regression analysis revealed that lower initial AMS (P = 0.000), longer duration after injury (P = 0.022) and injury above C4 level (P = 0.022) were factors predictive of lower final AMS. Longer duration (P = 0.020) and injury above C4 level (P = 0.010) were associated with a lower FIM MS. SF-36 scores were significantly lower in higher age (P = 0.015), female patients (P = 0.009) and patients with longer duration (P = 0.001). Conclusion: It is reasonable to consider surgical decompression in patients with cervical SCI in chronic stage and persistent spinal cord compression and/or gross cervical instability. Initial AMS, longer duration, injury above C4 level, higher age and female patients are the five major relevant factors of functional recovery. [ABSTRACT FROM AUTHOR]

L, M Western blotting to detect spinal cord apoptosis related protein expression Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Yuluo Rong, Chengyue Ji, Zhuanghui Wang and Xuhui Ge contributed equally to this work Correction to: J Neuroinflamm (2021) 18:196 https://doi.org/10.1186/s12974-021-02268-y Following publication of the original article [[1]], the author noticed that Figs. [Extracted from the article]

Background: To clarify the risk factors for subsidence of titanium mesh cage (TMC) following single-level anterior cervical corpectomy and fusion (ACCF) to reduce subsidence.Methods: The present retrospective cohort study included 73 consecutive patients who underwent single-level ACCF. Patients were divided into subsidence (n = 31) and non-subsidence groups (n = 42). Medical records and radiological parameters such as age, sex, operation level, segmental angle (SA), cervical sagittal angle (CSA), height of anterior (HAE) and posterior endplate (HPE), ratio of anterior (RAE) and posterior endplate (RPE), the alignment of TMC, the global cervical Hounsfield Units (HU) were analyzed. Clinical results were evaluated using the Japanese Orthopedic Association (JOA) scoring system and the Visual Analog Scale (VAS).Results: Subsidence occurred in 31 of 73 (42.5%) patients. Comparison between the groups showed significant differences in the value of RAE, the alignment of TMC and the global cervical HU value (p < 0.001, p = 0.002, p < 0.001). In multivariate logistic regression analysis, RAE > 1.18 (OR = 6.116, 95%CI = 1.613-23.192, p = 0.008), alignment of TMC > 3° (OR = 5.355, 95%CI = 1.474-19.454, p = 0.011) and the global cervical HU value< 333 (OR = 11.238, 95%CI = 2.844-44.413, p = 0.001) were independently associated with subsidence. Linear regression analysis revealed that RAE is significantly positive related to the extent of subsidence (r = - 0.502, p = 0.006).Conclusion: Our findings suggest that the value of RAE more than 1.18, alignment of TMC and poor bone mineral density are the risk factors for subsidence. TMC subsidence does not negatively affect the clinical outcomes after operation. Avoiding over expansion of intervertebral height, optimizing placing of TMC and initiation of anti-osteoporosis treatments 6 months prior to surgery might help surgeons to reduce subsidence after ACCF. [ABSTRACT FROM AUTHOR]

Simple Summary: The utilization of computer vision technology and automation for monitoring and collecting pigeon eggs is of significant importance for improving labor productivity and the breeding of egg-producing pigeons. Currently, research both domestically and internationally has predominantly focused on the detection of eggs from poultry such as chickens, ducks, and geese, leaving pigeon egg recognition largely unexplored. This study proposes an effective and lightweight network model, YOLOv8-PG, based on YOLOv8n, which maintains high detection accuracy while reducing the model's parameter count and computational load. This approach facilitates cost reduction in deployment and enhances feasibility for implementation on mobile robotic platforms. In response to the high breakage rate of pigeon eggs and the significant labor costs associated with egg-producing pigeon farming, this study proposes an improved YOLOv8-PG (real versus fake pigeon egg detection) model based on YOLOv8n. Specifically, the Bottleneck in the C2f module of the YOLOv8n backbone network and neck network are replaced with Fasternet-EMA Block and Fasternet Block, respectively. The Fasternet Block is designed based on PConv (Partial Convolution) to reduce model parameter count and computational load efficiently. Furthermore, the incorporation of the EMA (Efficient Multi-scale Attention) mechanism helps mitigate interference from complex environments on pigeon-egg feature-extraction capabilities. Additionally, Dysample, an ultra-lightweight and effective upsampler, is introduced into the neck network to further enhance performance with lower computational overhead. Finally, the EXPMA (exponential moving average) concept is employed to optimize the SlideLoss and propose the EMASlideLoss classification loss function, addressing the issue of imbalanced data samples and enhancing the model's robustness. The experimental results showed that the F1-score, mAP50-95, and mAP75 of YOLOv8-PG increased by 0.76%, 1.56%, and 4.45%, respectively, compared with the baseline YOLOv8n model. Moreover, the model's parameter count and computational load are reduced by 24.69% and 22.89%, respectively. Compared to detection models such as Faster R-CNN, YOLOv5s, YOLOv7, and YOLOv8s, YOLOv8-PG exhibits superior performance. Additionally, the reduction in parameter count and computational load contributes to lowering the model deployment costs and facilitates its implementation on mobile robotic platforms. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) has a very disabling central nervous system impact but currently lacks effective treatment. Bone marrow-derived macrophages (BMDMs) are recruited to the injured area after SCI and participate in the regulation of functional recovery with microglia. Previous studies have shown that M2 microglia-derived small extracellular vesicles (SEVs) have neuroprotective effects, but the effects of M2 BMDM-derived sEVs (M2 BMDM-sEVs) have not been reported in SCI treatment. Results: In this study, we investigated the role of M2 BMDM-sEVs in vivo and in vitro for SCI treatment and its mechanism. Our results indicated that M2 BMDM-sEVs promoted functional recovery after SCI and reduced neuronal apoptosis in mice. In addition, M2 BMDM-sEVs targeted mammalian target of rapamycin (mTOR) to enhance the autophagy level of neurons and reduce apoptosis. MicroRNA-421-3P (miR-421-3p) can bind to the 3′ untranslated region (3′UTR) of mTOR. MiR-421-3p mimics significantly reduced the activity of luciferase-mTOR 3′UTR constructs and increased autophagy. At the same time, tail vein injection of inhibitors of SEVs (Inh-sEVs), which were prepared by treatment with an miR-421-3p inhibitor, showed diminished protective autophagy of neuronal cells in vivo. Conclusions: In conclusion, M2 BMDM-sEVs inhibited the mTOR autophagy pathway by transmitting miR-421-3p, which reduced neuronal apoptosis and promoted functional recovery after SCI, suggesting that M2 BMDM-sEVs may be a potential therapy for SCI. [ABSTRACT FROM AUTHOR]

Background: Spinal cord ischemia reperfusion injury (SCIRI) is a complication of aortic aneurysm repair or spinal cord surgery that is associated with permanent neurological deficits. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have been shown to be potential therapeutic options for improving motor functions after SCIRI. Due to their easy access and multi-directional differentiation potential, adipose‐derived stem cells (ADSCs) are preferable for this application. However, the effects of ADSC-derived sEVs (ADSC-sEVs) on SCIRI have not been reported. Results: We found that ADSC-sEVs inhibited SCIRI-induced neuronal apoptosis, degradation of tight junction proteins and suppressed endoplasmic reticulum (ER) stress. However, in the presence of the ER stress inducer, tunicamycin, its anti-apoptotic and blood–spinal cord barrier (BSCB) protective effects were significantly reversed. We found that ADSC-sEVs contain tumor necrosis factor (TNF)-stimulated gene-6 (TSG-6) whose overexpression inhibited ER stress in vivo by modulating the PI3K/AKT pathway. Conclusions: ADSC-sEVs inhibit neuronal apoptosis and BSCB disruption in SCIRI by transmitting TSG-6, which suppresses ER stress by modulating the PI3K/AKT pathway. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a devastating trauma that leads to irreversible motor and sensory dysfunction and is, so far, without effective treatment. Recently, however, nano‐sized extracellular vesicles derived from preconditioned mesenchymal stem cells (MSCs) have shown great promise in treating various diseases, including SCI. In this study, we investigated whether extracellular vesicles (MEVs) derived from MSCs pretreated with melatonin (MT), which is well recognized to be useful in treating diseases, including Alzheimer's disease, non‐small cell lung cancer, acute ischemia‐reperfusion liver injury, chronic kidney disease, and SCI, are better able to promote functional recovery in mice after SCI than extracellular vesicles derived from MSCs without preconditioning (EVs). MEVs were found to facilitate motor behavioral recovery more than EVs and to increase microglia/macrophages polarization from M1‐like to M2‐like in mice. Experiments in BV2 microglia and RAW264.7 macrophages confirmed that MEVs facilitate M2‐like polarization and also showed that they reduce the production of reactive oxygen species (ROS) and regulate mitochondrial function. Proteomics analysis revealed that ubiquitin‐specific protease 29 (USP29) was markedly increased in MEVs, and knockdown of USP29 in MEVs (shUSP29‐MEVs) abolished MEVs‐mediated benefits in vitro and in vivo. We then showed that USP29 interacts with, deubiquitinates and therefore stabilizes nuclear factor‐like 2 (NRF2), thereby regulating microglia/macrophages polarization. In NRF2 knockout mice, MEVs failed to promote functional recovery and M2‐like microglia/macrophages polarization. We also showed that MT reduced global N6‐methyladenosine (m6A) modification and levels of the m6A "writer" methyltransferase‐like 3 (METTL3). The stability of USP29 mRNA in MSCs was enhanced by treatment with MT, but inhibited by overexpression of METTL3. This study describes a very promising extracellular vesicle‐based approach for treating SCI. [ABSTRACT FROM AUTHOR]

We performed a retrospective cohort study to investigate the prevalence of and risk factors for asymptomatic spondylotic cervical spinal stenosis (ASCSS) in the setting of lumbar spinal stenosis (LSS). A total of 114 patients with a diagnosis of LSS without cervical myelopathy and radiculopathy were grouped into ASCSS and non-ASCSS groups. The medical data and radiological parameters, including age, sex, body mass index, Charlson comorbidity index, symptom duration, redundant nerve roots, dural sac cross-sectional area (DCSA), facet joint angle, lumbar lordosis angle (LLA), pelvic incidence (PI), Torg-Pavlov ratio, and lumbosacral transitional vertebrae, were analyzed. The lumbar stenosis index and cervical stenosis index of the 114 patients were also analyzed. ASCSS occurred in 70 of the 114 patients with LSS (61.4%). The two groups showed significant differences in symptom duration, redundant nerve roots, LLA, DCSA, and PI. On multivariate logistic regression analysis, an LLA >35.85° (P < 0.001) and a DCSA <84.50 mm2 (P = 0.003) were independently associated with ASCSS. The multi-index receiver operating characteristic curve showed that the area under the curve for predicted probability was 0.805 (P < 0.001). Linear regression analysis revealed that cervical stenosis index significantly and positively correlated with the lumbar stenosis index (r = 0.430; P < 0.001). Our findings suggest that an LLA >35.85° and a DCSA <84.50 mm2 are risk factors for the development of ASCSS. For LSS patients with an enlarged LLA and reduced DSCA, a whole spinal magnetic resonance imaging examination should be performed. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) is a catastrophic injury that can cause irreversible motor dysfunction with high disability. Exosomes participate in the transport of miRNAs and play an essential role in intercellular communication via transfer of genetic material. However, the miRNAs in exosomes which derived from neurons, and the underlying mechanisms by which they contribute to SCI remain unknown. Methods: A contusive in vivo SCI model and a series of in vitro experiments were carried out to explore the therapeutic effects of exosomes. Then, a miRNA microarray analysis and rescue experiments were performed to confirm the role of neuron-derived exosomal miRNA in SCI. Western blot, luciferase activity assay, and RNA-ChIP were used to investigate the underlying mechanisms. Results: The results indicated that neuron-derived exosomes promoted functional behavioral recovery by suppressing the activation of M1 microglia and A1 astrocytes in vivo and in vitro. A miRNA array showed miR-124-3p to be the most enriched in neuron-derived exosomes. MYH9 was identified as the target downstream gene of miR-124-3p. A series of experiments were used to confirm the miR-124-3p/MYH9 axis. Finally, it was found that PI3K/AKT/NF-κB signaling cascades may be involved in the modulation of microglia by exosomal miR-124-3p. Conclusion: A combination of miRNAs and neuron-derived exosomes may be a promising, minimally invasive approach for the treatment of SCI. [ABSTRACT FROM AUTHOR]

Background: Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction with high disability and mortality. In recent years, mesenchymal stem cell (MSC)-secreted nano-sized exosomes have shown great potential for promoting functional behavioral recovery following SCI. However, MSCs are usually exposed to normoxia in vitro, which differs greatly from the hypoxic micro-environment in vivo. Thus, the main purpose of this study was to determine whether exosomes derived from MSCs under hypoxia (HExos) exhibit greater effects on functional behavioral recovery than those under normoxia (Exos) following SCI in mice and to seek the underlying mechanism.Methods: Electron microscope, nanoparticle tracking analysis (NTA), and western blot were applied to characterize differences between Exos and HExos group. A SCI model in vivo and a series of in vitro experiments were performed to compare the therapeutic effects between the two groups. Next, a miRNA microarray analysis was performed and a series of rescue experiments were conducted to verify the role of hypoxic exosomal miRNA in SCI. Western blot, luciferase activity, and RNA-ChIP were used to investigate the underlying mechanisms.Results: Our results indicate that HExos promote functional behavioral recovery by shifting microglial polarization from M1 to M2 phenotype in vivo and in vitro. A miRNA array showed miR-216a-5p to be the most enriched in HExos and potentially involved in HExos-mediated microglial polarization. TLR4 was identified as the target downstream gene of miR-216a-5p and the miR-216a-5p/TLR4 axis was confirmed by a series of gain- and loss-of-function experiments. Finally, we found that TLR4/NF-κB/PI3K/AKT signaling cascades may be involved in the modulation of microglial polarization by hypoxic exosomal miR-216a-5p.Conclusion: Hypoxia preconditioning represents a promising and effective approach to optimize the therapeutic actions of MSC-derived exosomes and a combination of MSC-derived exosomes and miRNAs may present a minimally invasive method for treating SCI. [ABSTRACT FROM AUTHOR]