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Spinal cord injury (SCI) leads to loss of motor and sensory function below the injury level and imposes a considerable burden on patients, families, and society. Repair of the injured spinal cord has been recognized as a global medical challenge for many years. Significant progress has been made in research on the pathological mechanism of spinal cord injury. In particular, with the development of gene regulation, cell sequencing, and cell tracing technologies, in-depth explorations of the SCI microenvironment have become more feasible. However, translational studies related to repair of the injured spinal cord have not yielded significant results. This review summarizes the latest research progress on two aspects of SCI pathology: intraneuronal microenvironment imbalance and regenerative microenvironment imbalance. We also review repair strategies for the injured spinal cord based on microenvironment imbalance, including medications, cell transplantation, exosomes, tissue engineering, cell reprogramming, and rehabilitation. The current state of translational research on SCI and future directions are also discussed. The development of a combined, precise, and multitemporal strategy for repairing the injured spinal cord is a potential future direction.

Spinal cord injury (SCI), for which there currently is no cure, is a heavy burden on patient physiology and psychology. The microenvironment of the injured spinal cord is complicated. According to our previous work and the advancements in SCI research, ‘microenvironment imbalance’ is the main cause of the poor regeneration and recovery of SCI. Microenvironment imbalance is defined as an increase in inhibitory factors and decrease in promoting factors for tissues, cells and molecules at different times and spaces. There are imbalance of hemorrhage and ischemia, glial scar formation, demyelination and re-myelination at the tissue’s level. The cellular level imbalance involves an imbalance in the differentiation of endogenous stem cells and the transformation phenotypes of microglia and macrophages. The molecular level includes an imbalance of neurotrophic factors and their pro-peptides, cytokines, and chemokines. The imbalanced microenvironment of the spinal cord impairs regeneration and functional recovery. This review will aid in the understanding of the pathological processes involved in and the development of comprehensive treatments for SCI.

ObjectivesTo evaluate the most up-to-date burden of traumatic brain injury (TBI) and spinal cord injury (SCI) and analyse their leading causes in different countries/territories.DesignAn analysis of Global Burden of Disease (GBD) data.SettingThe epidemiological data were gathered from GBD Results Tool (1 January, 1990─31 December 2019) covering 21 GBD regions and 204 countries/ territories.ParticipantsPatients with TBI/SCI.Main outcomes and measuresAbsolute numbers and age-standardised rates/estimates of incidence, prevalence and years lived with disability (YLDs) of TBI/SCI by location in 2019, with their percentage changes from 1990 to 2019. The leading causes (eg, falls) of TBI/SCI in 204 countries/territories.ResultsGlobally, in 2019, TBI had 27.16 million new cases, 48.99 million prevalent cases and 7.08 million YLDs. SCI had 0.91 million new cases, 20.64 million prevalent cases and 6.20 million YLDs. Global age-standardised incidence rates of TBI decreased significantly by −5.5% (95% uncertainty interval −8.9% to −3.0%) from 1990 to 2019, whereas SCI had no significant change (−6.1% (−17.3% to 1.5%)). Regionally, in 2019, Eastern Europe and High-income North America had the highest burden of TBI and SCI, respectively. Nationally, in 2019, Slovenia and Afghanistan had the highest age-standardised incidence rates of TBI and SCI, respectively. For TBI, falls were the leading cause in 74% (150/204) of countries/territories, followed by pedestrian road injuries (14%, 29/204), motor vehicle road injuries (5%, 11/204), and conflict and terrorism (2%, 4/204). For SCI, falls were the leading cause in 97% (198/204) of countries/territories, followed by conflict and terrorism (3%, 6/204).ConclusionsGlobal age-standardised incidence rates of TBI have decreased significantly since 1990, whereas SCI had no significant change. The leading causes of TBI/SCI globally were falls, but variations did exist between countries/territories. Policy-makers should continue to prioritise interventions to reduce falls, but priorities may vary between countries/territories.

Zwitterionic hydrogels exhibit eminent nonfouling and hemocompatibility. Several key challenges hinder their application as coating materials for blood-contacting biomedical devices, including weak mechanical strength and low adhesion to the substrate. Here, we report a poly(carboxybetaine) microgel reinforced poly(sulfobetaine) (pCBM/pSB) pure zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties. The pCBM/pSB hydrogel coating was bonded to the PVC substrate via the entanglement network between the pSB and PVC chain. Moreover, the pCBM/pSB hydrogel coating can maintain favorable stability even after 21 d PBS shearing, 0.5 h strong water flushing, 1000 underwater bends, and 100 sandpaper abrasions. Notably, the pCBM/pSB hydrogel coated PVC tubing can not only mitigate the foreign body response but also prevent thrombus formation ex vivo in rats and rabbits blood circulation without anticoagulants. This work provides new insights to guide the design of pure zwitterionic hydrogel coatings for biomedical devices. Zwitterionic hydrogels are nonfouling and hemocompatibility but several key challenges such as weak mechanical strength and low adhesion hamper their application as coating materials for devices. Here, the authors report a microgel reinforced zwitterionic hydrogel with excellent mechanical robustness and anti-swelling properties.

Macrophage/microglia polarization acts as an important part in regulating inflammatory responses in spinal cord injury (SCI). However, the regulation of inflammation of Schwann cell-derived exosomes (SCDEs) for SCI repair is still unclear. Therefore, we intend to find out the effect of SCDEs on regulating the inflammation related to macrophage polarization during the recovery of SCI. Firstly, the thesis demonstrated that SCDEs could attenuate the LPS- inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization. Similarly, SCDEs improved functional recovery of female Wistar rats of the SCI contusion model according to BBB (Basso, Beattie, and Bresnahan) score, electrophysiological assay, and the gait analysis system of CatWalk XT. Moreover, MFG-E8 was verified as the main component of SCDEs to improve the inflammatory response by proteomic sequencing and lentiviral transfection. Improvement of the inflammatory microenvironment also inhibited neuronal apoptosis. The knockout of MFG-E8 in SCs can reverse the anti-inflammatory effects of SCDEs treatment. The SOCS3/STAT3 signaling pathway was identified to participate in upregulating M2 polarization induced by MFG-E8. In conclusion, our findings will enrich the mechanism of SCDEs in repairing SCI and provide potential applications and new insights for the clinical translation of SCDEs treatment for SCI.

Spinal cord injury (SCI) is catastrophic to humans and society. However, there is currently no effective treatment for SCI. Autophagy is known to serve critical roles in both the physiological and pathological processes of the body, but its facilitatory and/or deleterious effects in SCI are yet to be completely elucidated. This study aimed to use primary Schwann cell-derived exosomes (SCDEs) to treat rats after SCI. In the present study, SCDEs were purified and their efficacy in ameliorating the components of SCI was examined. Using both in vivo and in vitro experiments, it was demonstrated that SCDEs increased autophagy and decreased apoptosis after SCI, which promoted axonal protection and the recovery of motor function. Furthermore, it was discovered that an increased number of SCDEs resulted in a decreased expression level of EGFR, which subsequently inhibited the Akt/mTOR signaling pathway, which upregulated the level of autophagy to ultimately induce microtubule acetylation and polymerization. Collectively, the present study identified that SCDEs could induce axonal protection after SCI by increasing autophagy and decreasing apoptosis, and it was suggested that this may involve the EGFR/Akt/mTOR signaling pathway.

Background Traumatic spinal cord injury (SCI) is a severely disabling disease that leads to loss of sensation, motor, and autonomic function. As exosomes have great potential in diagnosis, prognosis, and treatment of SCI because of their ability to easily cross the blood–brain barrier, the function of Schwann cell-derived exosomes (SCDEs) is still largely unknown. Methods A T10 spinal cord contusion was established in adult female mice. SCDEs were injected into the tail veins of mice three times a week for 4 weeks after the induction of SCI, and the control group was injected with PBS. High-resolution transmission electron microscope and western blot were used to characterize the SCDEs. Toll-like receptor 2 (TLR2) expression on astrocytes, chondroitin sulfate proteoglycans (CSPGs) deposition and neurological function recovery were measured in the spinal cord tissues of each group by immunofluorescence staining of TLR2, GFAP, CS56, 5-HT, and β-III-tublin, respectively. TLR2 f/f mice were crossed to the GFAP-Cre strain to generate astrocyte specific TLR2 knockout mice (TLR2 −/− ). Finally, western blot analysis was used to determine the expression of signaling proteins and IKKβ inhibitor SC-514 was used to validate the involved signaling pathway. Results Here, we found that TLR2 increased significantly on astrocytes post-SCI. SCDEs treatment can promote functional recovery and induce the expression of TLR2 on astrocytes accompanied with decreased CSPGs deposition. The specific knockout of TLR2 on astrocytes abolished the decreasing CSPGs deposition and neurological functional recovery post-SCI. In addition, the signaling pathway of NF-κB/PI3K involved in the TLR2 activation was validated by western blot. Furthermore, IKKβ inhibitor SC-514 was also used to validate this signaling pathway. Conclusion Thus, our results uncovered that SCDEs can promote functional recovery of mice post-SCI by decreasing the CSPGs deposition via increasing the TLR2 expression on astrocytes through NF-κB/PI3K signaling pathway.

As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body's natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs) and adipose-derived stem cells (ADSCs) as seed cells and introduced them into a silk fibroin (SF)/collagen scaffold to construct a tissue-engineered nerve conduit (TENC). Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft) were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.

Background Intervertebral disc herniation, degenerative lumbar spinal stenosis, and other lumbar spine diseases can occur across most age groups. MRI examination is the most commonly used detection method for lumbar spine lesions with its good soft tissue image resolution. However, the diagnosis accuracy is highly dependent on the experience of the diagnostician, leading to subjective errors caused by diagnosticians or differences in diagnostic criteria for multi-center studies in different hospitals, and inefficient diagnosis. These factors necessitate the standardized interpretation and automated classification of lumbar spine MRI to achieve objective consistency. In this research, a deep learning network based on SAFNet is proposed to solve the above challenges. Methods In this research, low-level features, mid-level features, and high-level features of spine MRI are extracted. ASPP is used to process the high-level features. The multi-scale feature fusion method is used to increase the scene perception ability of the low-level features and mid-level features. The high-level features are further processed using global adaptive pooling and Sigmoid function to obtain new high-level features. The processed high-level features are then point-multiplied with the mid-level features and low-level features to obtain new high-level features. The new high-level features, low-level features, and mid-level features are all sampled to the same size and concatenated in the channel dimension to output the final result. Results The DSC of SAFNet for segmenting 17 vertebral structures among 5 folds are 79.46 ± 4.63%, 78.82 ± 7.97%, 81.32 ± 3.45%, 80.56 ± 5.47%, and 80.83 ± 3.48%, with an average DSC of 80.32 ± 5.00%. The average DSC was 80.32 ± 5.00%. Compared to existing methods, our SAFNet provides better segmentation results and has important implications for the diagnosis of spinal and lumbar diseases. Conclusions This research proposes SAFNet, a highly accurate and robust spine segmentation deep learning network capable of providing effective anatomical segmentation for diagnostic purposes. The results demonstrate the effectiveness of the proposed method and its potential for improving radiological diagnosis accuracy.

Spinal cord injury (SCI) results in significant neural damage and inhibition of axonal regeneration due to an imbalanced microenvironment. Extensive evidence supports the efficacy of mesenchymal stem cell (MSC) transplantation as a therapeutic approach for SCI. This review aims to present an overview of MSC regulation on the imbalanced microenvironment following SCI, specifically focusing on inflammation, neurotrophy and axonal regeneration. The application, limitations and future prospects of MSC transplantation are discussed as well. Generally, a comprehensive perspective is provided for the clinical translation of MSC transplantation for SCI.