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Antimony smelting activities damage the soil and vegetation surroundings while generating economic value. However, no standardized methods are available to diagnose the extent of soil degradation at antimony smelting sites. This study developed a standardized framework for assessing soil quality by considering microbial-induced resilience and heavy metal contamination at Xikuangshan antimony smelting site. The soil resilience index (SRI) and soil contamination index (SCI) were calculated by Minimum Data Set and geo-accumulation model, respectively. After standardized by a multi-criteria quantitative procedure of modified Nemerow's pollution index (NPI), the integrated assessment of soil quality index (SQI), which is the minimum of SRINPI and SCINPI, was achieved. The results showed that Sb and As were the prominent metal(loid) pollutants, and significant correlations between SQI and SRI indicated that the poor soil quality was mainly caused by the low level of soil resilience. The primary limiting factors of SRI were Fungi in high and middle contaminated areas, and Skermanella in low contaminated area, suggesting that the weak soil resilience was caused by low specific microbial abundances. Microbial regulation and phytoremediation are greatly required to improve the soil quality at antimony smelting sites from the perspectives of pollution control and resilience improvement. This study improves our understanding of ecological effects of antimony smelting sites and provides a theoretical basis for ecological restoration and sustainable development of mining areas.

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In vertebrates, many organs, such as the kidney and the mammary gland form ductal structures based on the folding of epithelial sheets. The development of these organs relies on coordinated sorting of different cell lineages in both time and space, through mechanisms that remain largely unclear. Tissues are composed of several cell types with distinct biomechanical properties, particularly at cell-cell and cell-substrate boundaries. One hypothesis is that adjacent epithelial layers work in a coordinated manner to shape the tissue. Using in vitro experiments on model epithelial cells, differential expression of atypical Protein Kinase C iota (aPKCi), a key junctional polarity protein, is shown to reinforce cell epithelialization and trigger sorting by tuning cell mechanical properties at the tissue level. In a broader perspective, it is shown that in a heterogeneous epithelial monolayer, in which cell sorting occurs, forces arising from epithelial cell growth under confinement by surrounding cells with different biomechanical properties are sufficient to promote collective cell extrusion and generate emerging 3D organization related to spheroids and buds. Overall, this research sheds light on the role of aPKCi and the biomechanical interplay between distinct epithelial cell lineages in shaping tissue organization, providing insights into the understanding of tissue and organ development.

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Background: Thoracolumbar transcutaneous spinal cord stimulation (tSCS) non-invasively evokes posterior root-muscle reflexes (PRMR) with the aim of neuromodulating sensorimotor function following spinal cord injury. Research is still in its infancy regarding the effect of body position on the nature of these spinally evoked responses. Therefore, the aim of this study was to investigate the influence of body position on the nature of PRMR responses during tSCS. Methods: A total of 11 (6M, 5F) participants completed a full PRMR recruitment curve from 10 ma up to 120 ma (10 ma increments) at the T11/12 intervertebral space using a singular 3.2 cm diameter cathode. At each intensity, three paired pulses (50 ms inter-pulse interval), followed by three singular pulses with a six-second delay were applied in each body position (supine, supine 90-90, sitting and standing) in a randomised order. The PRMR responses in lower limb muscles were recorded using wireless electromyographic sensors placed on the Soleus, Tibialis Anterior, Rectus Femoris and Bicep Femoris long head. A two-way (body position × muscle) repeated measures analysis of variance was used to investigate the effect of body position on PRMR-evoked responses. Results: There was a significant main effect of body position on PRMR resting motor threshold (RMT) (p < 0.001), first response peak-to-peak amplitude (p = 0.003) and percentage post-activation depression (%PAD) (p = 0.012). Sitting had significantly higher RMT and significantly lower first response peak-to-peak amplitudes compared to all other positions, but significant differences in %PAD were only detectible between supine and standing. Conclusions: Body position influences the nature of PRMR-evoked responses during tSCS.

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PURPOSE: To describe the prevalence of nocturia and obstructive sleep apnea (OSA) in a cohort of spinal cord injury (SCI) patients and to describe their association. Additionally, to assess clinical and urodynamic data explaining nocturia and to evaluate the effect of OSA management with continuous positive airway pressure (CPAP). METHOD: Retrospective analysis of data from patients with SCI followed in a tertiary care rehabilitation center with a specialized sleep and neuro-urology units. All adult SCI patients who underwent urodynamic assessment before polysomnography (PSG) between 2015 and 2023 were eligible. Subjective (nocturia) and objective data (urodynamic data, polysomnography, CPAP built-in software) were collated from the Handisom database (database register no. 20200224113128) and the medical records of SCI patients. Statistical testing used Mann-Whitney test for non-parametric variables, Fisher's exact test for contingency analysis and the Spearman correlation test to assess correlations. A p-value < 0.05 was considered significant. Statistical analyses were performed using GraphPad Prism v9. RESULTS: 173 patients (131 males, 42 females) were included. The majority of patients were paraplegic (n = 111 (64,2%)) and had complete lesions (n = 75 (43,4%)). A total of 100 patients had nocturia (57,5%). The prevalence of OSA (Apnea Hypopnea Index (AHI) ≥ 15/h) in the studied population was 61,9%. No correlation was found between nocturia and OSA. A significant difference was observed between patients with and without nocturia in terms of the presence of neurogenic detrusor overactivity (p = 0,049), volume at the first detrusor contraction (p = 0,004) and the bladder functional capacity (p < 0,001). CONCLUSION: Nocturia and OSA are highly prevalent in patients with SCI, but no statistical association was found between these two disorders. A prospective study focusing on nocturnal polyuria will be needed to assess the impact of OSA on lower urinary tract symptoms in SCI patients.

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BACKGROUND: Sonic Hedgehog (Shh), extensively researched for its role in early neurogenesis and brain development, has recently been recognized for its neuroprotective potential following neuronal injuries. This study examines the immediate impact of early administered Shh on the local inflammatory response post-acute spinal cord injury in rats. METHODS: Thirty-four female Wistar rats underwent either sham surgery (laminectomy; n = 10) or clip compression/contusion spinal cord injury (SCI) at the T9 level. This was followed by implantation of an osmotic pump and a subdural catheter for continuous intrathecal delivery of Shh (n = 12) or placebo (NaCl; n = 12). Locomotor function was assessed at 3- and 7-days post-injury (dpi) using the Basso, Beattie, and Bresnahan (BBB) score and the Gridwalk test. Animals were euthanized after 3 or 7 days for immunohistochemical analysis of the local inflammatory reaction and immune cell migration. RESULTS: Shh-treated rats demonstrated significant hindlimb movement and coordination improvements at 7 days post-injury, compared to controls. This enhancement was accompanied by a significant reduction in both immune cell presence and blood plasma products within spinal cord lesions, suggesting Shh's dual role in modulating immune cell migration and maintaining the integrity of the blood-spinal cord barrier. Separately, these Shh-treated rats also showed an increase in M(IL-4) polarization of macrophages, further underlining the potential therapeutic impact of Shh in post-injury recovery. Notably, these effects were not evident at three days post-injury. CONCLUSION: Shh application at 7 days post-injury showed immunomodulatory effects, possibly via enhanced blood-spinal cord barrier integrity, reduced immune cell migration, and increased anti-inflammatory immune cell differentiation. These mechanisms collectively contribute to enhanced locomotor recovery.

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Transplanted mesenchymal stem cells (MSCs) can significantly aid in repairing spinal cord injuries (SCI) by migrating to and settling at the injury site. However, this process is typically inefficient, as only a small fraction of MSCs successfully reach the target lesion area. During SCI, the increased expression and secretion of hepatocyte growth factor (HGF) act as a chemoattractant that guides MSC migration. Nonetheless, the precise mechanisms by which HGF influences MSC migration are not fully understood. This study focused on unraveling the molecular pathways that drive MSC migration towards the SCI site in response to HGF. It was found that HGF can activate ß-catenin signaling in MSCs either by phosphorylating LRP6 or by suppressing GSK3ß phosphorylation through the AKT and ERK1/2 pathways, or by enhancing the expression and nuclear translocation of TCF4. This activation leads to elevated Nedd9 expression, which promotes focal adhesion formation and F-actin polymerization, facilitating chemotactic migration. Transplanting MSCs during peak HGF expression in injured tissues substantially improves nerve regeneration, reduces scarring, and enhances hind limb mobility. Additionally, prolonging HGF release can further boost MSC migration and engraftment, thereby amplifying regenerative outcomes. However, inhibiting HGF/Met or interfering with ß-catenin or Nedd9 signaling significantly impairs MSC engraftment, obstructing tissue repair and functional recovery. Together, these findings provide a theoretical basis and practical strategy for MSC transplantation therapy in SCI, highlighting the specific molecular mechanisms by which HGF regulates ß-catenin signaling in MSCs, ultimately triggering their chemotactic migration.

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INTRODUCTION: Spinal cord injury (SCI) may bring lifelong consequences for affected patients and a high financial burden to the health care system. SOURCE OF DATA: Published peer-reviewed scientific articles identified from EMBASE, Google Scholar, PubMed and Scopus. AREAS OF AGREEMENT: Surgery and blood pressure management are the main targets in acute SCI to avoid secondary damage. AREAS OF CONTROVERSY: The management of secondary chronic SCI is challenging, with unpredictable outcomes. GROWING POINTS: Given the lack of consensus on pharmacological therapy for acute and secondary chronic SCI, the present study analyses the currently available drugs and treatment options to manage secondary chronic SCI. AREAS TIMELY FOR DEVELOPING RESEARCH: Different approaches exist for the pharmacological management of secondary chronic SCI. One of the most investigated drugs, 4-aminopyridine, improves central motor conduction and shows improvement in neurological signs. Positive results in different areas have been observed in patients receiving the anti-spastic drugs tizanidine and baclofen or Granulocyte colony-stimulating factor. Growth hormone showed only minimal or no significant effects, and the therapy of secondary chronic SCI with riluzole has been poorly researched to date.

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Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.

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Background: Knowledge is still lacking regarding the preferred method for evaluation of learning in the Rey Auditory Verbal Learning Test (RAVLT). Validity of different methods was examined by the effect size in differentiating diagnostic stages in memory clinic patients versus healthy adults and the strength of association between RAVLT performance and brain atrophy. Method: The study included individuals with dementia (n = 247), Mild Cognitive Impairment (MCI, n = 709), Subjective Cognitive Impairment (SCI, n = 175) and cognitively unimpaired adults serving as healthy controls (HC, n = 102). All patients went through a comprehensive clinical examination and neuropsychological assessment of cognition including episodic memory gauged with RAVLT and brain imaging of medial temporal atrophy, cortical atrophy, and white matter hyperintensity. Results: The standard method for evaluation of learning in RAVLT (summed score over five trials) together with the late learning method (mean of trials 4 and 5) were the two most powerful methods according to group differentiation (discriminant validity). Both methods also showed considerable association with medial temporal atrophy (construct validity). The initial RAVLT performance represented by results on trial 1 and the constant in regression analysis with the power function provided information regarding attention that was important for the separation of SCI and HC. Conclusions: The most favorable clinical utility was indicated by discriminant and construct validity by total learning (standard method) including both attention- and learning-related parts and late learning of RAVLT performance, while theoretical understanding of mental processes involved in RAVLT performance was provided by the distinction between initial versus the subsequent learning performance.

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INTRODUCTION: An acute spinal cord injury (SCI) results in significant morbidity worldwide. Guidelines recommend mean arterial pressure (MAP) augmentation to prevent hypoperfusion. Although there is no consensus on a single vasoactive agent for MAP augmentation, intravenous vasopressors are commonly utilized, requiring an intensive care unit (ICU). Beyond the financial burden for patients, ICU stays require significant hospital system resource utilization. Oral vasoactive agents, such as pseudoephedrine and midodrine, are also utilized for MAP augmentation, but little data on their efficacy are available. This study investigates the use and dosing of oral vasoactive agents as an alternative in MAP augmentation in SCI. MATERIALS AND METHODS: Adult SCI patients were retrospectively investigated. Total daily vasoactive dose, treatment efficacy, and ICU length of stay were evaluated. RESULTS: 141 patients were evaluated, with 7.1% receiving oral agents alone, and 80.9% receiving vasopressors who either transitioned to pseudoephedrine, pseudoephedrine plus midodrine, or no oral agent. Patients receiving oral agents trended toward decreased ICU stay, but there was no difference in vasopressor duration. Similar MAP goal success rates were found between groups. A variety of initial and maximum daily doses of PO agents were used. Median doses were 120 mg pseudoephedrine and 30 mg midodrine. Early initiation of pseudoephedrine resulted in shorter ICU stays. CONCLUSIONS: This study demonstrated shorter ICU length of stay and similar MAP goal success with PO agents as compared to vasopressors. This may indicate these medications could be utilized to decrease the financial burden placed on patients and the health care system from lengthy ICU courses. This study is limited by a small sample size and variable agent dosing.

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Though spinal cord injury (SCI) causes irreversible sensory and motor impairments in human, adult zebrafish retain the potent regenerative capacity by injury-induced proliferation of central nervous system (CNS)-resident progenitor cells to develop new functional neurons at the lesion site. The hallmark of SCI in zebrafish lies in a series of changes in the epigenetic landscape, specifically DNA methylation and histone modifications. Decoding the post-SCI epigenetic modifications is therefore critical for the development of therapeutic remedies that boost SCI recovery process. Here, we have studied on Sirtuin1 (Sirt1), a non-classical histone deacetylase that potentially plays a critical role in neural progenitor cells (NPC) proliferation and axonal regrowth following SCI in zebrafish. We investigated the role of Sirt1 in NPC proliferation and axonal regrowth in response to injury in the regenerating spinal cord and found that Sirt1 is involved in the induction of NPC proliferation along with glial bridging during spinal cord regeneration. We also demonstrate that Sirt1 plays a pivotal role in regulating the HIPPO pathway through deacetylation-mediated inactivation of Dnmt1 and subsequent hypomethylation of yap1 promoter, leading to the induction of ctgfa expression, which drives the NPC proliferation and axonal regrowth to complete the regenerative process. In conclusion, our study reveals a novel cross-talk between two important epigenetic effectors, Sirt1 and Dnmt1, in the context of spinal cord regeneration, establishing a previously undisclosed relation between Sirt1 and Yap1 which provides a deeper understanding of the underlying mechanisms governing injury-induced NPC proliferation and axonal regrowth. Therefore, we have identified Sirt1 as a novel, major epigenetic regulator of spinal cord regeneration by modulating the HIPPO pathway in zebrafish.

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Spinal cord injury (SCI) is a central nervous system injury that leads to neurological dysfunction or paralysis, which seriously affects patients' quality of life and causes a heavy social and economic burden. The pathological mechanism of SCI has not been fully revealed, resulting in unsatisfactory clinical treatment. Therefore, more research is urgently needed to reveal its precise pathological mechanism. Numerous studies have shown that inflammation is closely related to various pathological processes in SCI. Inflammatory response is an important pathological process leading to secondary injury, and sustained inflammatory response can exacerbate the injury and hinder the recovery of neurological function after injury. Epigenetic modification is considered to be an important regulatory mechanism in the pathological process of many diseases. Epigenetic modification mainly affects the function and characteristics of genes through the reversibility of mechanisms such as DNA methylation, histone modification, and regulation of non-coding RNA, thus having a significant impact on the pathological process of diseases and the survival state of the body. Recently, the role of epigenetic modification in the inflammatory response of SCI has gradually entered the field of view of researchers, and epigenetic modification may be a potential means to treat SCI. In this paper, we review the effects and mechanisms of different types of epigenetic modifications (including histone modifications, DNA methylation, and non-coding RNAs) on post-SCI inflammation and their potential therapeutic effects on inflammation to improve our understanding of the secondary SCI stage. This review aims to help identify new markers, signaling pathways and targeted drugs, and provide theoretical basis and new strategies for the diagnosis and treatment of SCI.

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Spinal cord injury (SCI) is a serious, disabling injury to the central nervous system that can lead to motor, sensory, and autonomic dysfunction below the injury plane. SCI can be divided into primary injury and secondary injury according to its pathophysiological process. Primary injury is irreversible in most cases, while secondary injury is a dynamic regulatory process. Secondary injury involves a series of pathological events, such as ischemia, oxidative stress, inflammatory events, apoptotic pathways, and motor dysfunction. Among them, oxidative stress is an important pathological event of secondary injury. Oxidative stress causes a series of destructive events such as lipid peroxidation, DNA damage, inflammation, and cell death, which further worsens the microenvironment of the injured site and leads to neurological dysfunction. The nuclear factor erythrocyte 2-associated factor 2 (Nrf2) is considered to be a key pathway of antioxidative stress and is closely related to the pathological process of SCI. Activation of this pathway can effectively inhibit the oxidative stress process and promote the recovery of nerve function after SCI. Therefore, the Nrf2 pathway may be a potential therapeutic target for SCI. This review deeply analyzed the generation of oxidative stress in SCI, the role and mechanism of Nrf2 as the main regulator of antioxidant stress in SCI, and the influence of cross-talk between Nrf2 and related pathways that may be involved in the pathological regulation of SCI on oxidative stress, and summarized the drugs and other treatment methods based on Nrf2 pathway regulation. The objective of this paper is to provide evidence for the role of Nrf2 activation in SCI and to highlight the important role of Nrf2 in alleviating SCI by elucidating the mechanism, so as to provide a theoretical basis for targeting Nrf2 pathway as a therapy for SCI.

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CONTEXT: Change in ability realization reflects the main contribution of rehabilitation to improvement in the performance of daily activities after spinal cord lesions (SCL). OBJECTIVE: To adapt a Spinal Cord Ability Realization Measurement Index (SCI-ARMI) formula to the new Spinal Cord Independence Measure version 4 (SCIM4). METHODS: Using data from 156 individuals for whom American Spinal Injury Association Motor Score (AMS) and SCIM4 scores were collected, we obtained an estimate for the highest possible SCIM4 given the patient's AMS value, using the 95th percentile of SCIM4 values at discharge from rehabilitation (SCIM95) for patients with any given AMS at discharge. We used the statistical software environment R to implement the quantile regression method for linear and quadratic formulas. We also compared the computed model with the SCIM95 model obtained using data from the present study group, positioned in the SCIM95 formula developed for SCIM3. RESULTS: The coefficients of the computed SCIM95 formula based on SCIM4 scores were statistically non-significant, which hypothetically reflects the small sample relative to the goal of estimating SCIM4 95th percentile. Predicting the ability using SCIM4 scores positioned in the SCIM95 formula used for SCIM3, however, yielded SCIM95 values, which are very close to those of the new SCIM95 formula (Mean difference 2.16, 95% CI = 1.45, 4.90). CONCLUSION: The SCI-ARMI formula, which is based on the SCIM95 formula developed for SCIM3, is appropriate for estimating SCI-ARMI at present, when SCIM4 scores are available. When sufficient additional data accumulates, it will be appropriate to introduce a modified SCI-ARMI formula.

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Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

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Translation of spinal cord injury (SCI) therapeutics from pre-clinical animal studies into human studies is challenged by effect size variability, irreproducibility, and misalignment of evidence used by pre-clinical versus clinical literature. Clinical literature values reproducibility, with the highest grade evidence (class 1) consisting of meta-analysis demonstrating large therapeutic efficacy replicating across multiple studies. Conversely, pre-clinical literature values novelty over replication and lacks rigorous meta-analyses to assess reproducibility of effect sizes across multiple articles. Here, we applied modified clinical meta-analysis methods to pre-clinical studies, comparing effect sizes extracted from published literature to raw data on individual animals from these same studies. Literature-extracted data (LED) from numerical and graphical outcomes reported in publications were compared with individual animal data (IAD) deposited in a federally supported repository of SCI data. The animal groups from the IAD were matched with the same cohorts in the LED for a direct comparison. We applied random-effects meta-analysis to evaluate predictors of neuroconversion in LED versus IAD. We included publications with common injury models (contusive injuries) and standardized end-points (open field assessments). The extraction of data from 25 published articles yielded n = 1841 subjects, whereas IAD from these same articles included n = 2441 subjects. We observed differences in the number of experimental groups and animals per group, insufficient reporting of dropout animals, and missing information on experimental details. Meta-analysis revealed differences in effect sizes across LED versus IAD stratifications, for instance, severe injuries had the largest effect size in LED (standardized mean difference [SMD = 4.92]), but mild injuries had the largest effect size in IAD (SMD = 6.06). Publications with smaller sample sizes yielded larger effect sizes, while studies with larger sample sizes had smaller effects. The results demonstrate the feasibility of combining IAD analysis with traditional LED meta-analysis to assess effect size reproducibility in SCI.

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Spinal cord injury is associated with skeletal unloading, sedentary behavior, decreases in skeletal muscle mass, and exercise intolerance, which results in rapid and severe bone loss. To date, monotherapy with physical interventions such as weight-bearing in standing frames, computer-controlled electrically stimulated cycling and ambulation exercise, and low-intensity vibration are unsuccessful in maintaining bone density after SCI. Strategies to maintain bone density with commonly used osteoporosis medications also fail to provide a significant clinical benefit, potentially due to a unique pathology of bone deterioration in SCI. In this review, the available data is discussed on evaluating and monitoring bone loss, fracture, and physical and pharmacological therapeutic approaches to SCI-associated disease of the skeleton. The treatment of SCI-associated disease of the skeleton, the implications for clinical management, and areas of need are considered for future investigation.

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PURPOSE: Repair of pararenal aneurysms poses a challenge, especially in an urgent setting. Despite the minimally invasive nature of the fenestrated/branched endovascular aortic repair, the technique may require extensive coverage of the aorta, increasing the risk of spinal cord ischemia. TECHNIQUE: A 68-year-old man was admitted with a rapid enlargement of an asymptomatic juxtarenal aortic aneurysm. A minimally invasive treatment with an off-the-shelf branched endovascular graft was planned. Before completing the aneurysm exclusion, an angiography highlighted a large lumbar artery, potentially significant for the perfusion of the spinal cord collateral network. Owing to this finding and an unsuccessful placement of the cerebrospinal fluid drainage, the procedure was staged and completed 5 days later using a physician-modified iliac branch device (IBD) for the segmental artery. The device was shortened and reversely loaded to obtain a cranially-oriented branch. A balloon-expandable covered stent was used to connect the retrograde branch (8 mm) to the lumbar artery (4 mm). Pre-discharge computed tomography (CT)-angiography confirmed the vessel patency. No neurological symptoms occurred. CONCLUSION: The use of a reversely-loaded IBD for segmental artery preservation appears feasible and safe. CLINICAL IMPACT: Intraoperative modification of an iliac branch device during an urgent branched endovascular aortic repair enabled preservation of a potentially critical segmental artery, thus reducing the risk of spinal cord ischemia. This adaptive interventional technique may also offer a strategy for preserving other anatomically significant vessels, such as accessory renal arteries, during complex aortic reconstructions in urgent settings.

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Spinal cord injury (SCI) is a complex tissue injury that results in a wide range of physical deficits, including permanent or progressive disabilities of sensory, motor and autonomic functions. To date, limitations in current clinical treatment options can leave SCI patients with lifelong disabilities. There is an urgent need to develop new therapies for reconstructing the damaged spinal cord neuron-glia network and restoring connectivity with the supraspinal pathways. Neural stem cells (NSCs) possess the ability to self-renew and differentiate into neurons and neuroglia, including oligodendrocytes, which are cells responsible for the formation and maintenance of the myelin sheath and the regeneration of demyelinated axons. For these properties, NSCs are considered to be a promising cell source for rebuilding damaged neural circuits and promoting myelin regeneration. Over the past decade, transplantation of NSCs has been extensively tested in a variety of preclinical models of SCI. This review aims to highlight the pathophysiology of SCI and promote the understanding of the role of NSCs in SCI repair therapy and the current advances in pathological mechanism, pre-clinical studies, as well as clinical trials of SCI via NSC transplantation therapeutic strategy. Understanding and mastering these frontier updates will pave the way for establishing novel therapeutic strategies to improve the quality of recovery from SCI.

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BACKGROUND: Spinal cord injury (SCI) is characterized by extensive demyelination and inflammatory responses. Facilitating the clearance of lipid droplets (LDs) within microglia contributes to creating a microenvironment that favors neural recovery and provides essential materials for subsequent remyelination. Therefore, investigating MicroRNAs (miRNAs) that regulate lipid homeostasis after SCI and elucidating their potential mechanisms in promoting LDs clearance in microglia have become focal points of SCI research. METHODS: We established a subacute C5 hemicontusion SCI model in mice and performed transcriptomic sequencing on the injury epicenter to identify differentially expressed genes and associated pathways. Confocal imaging was employed to observe LDs accumulation. Multi-omics analyses were conducted to identify differentially expressed mRNA and miRNA post-SCI. Pathway enrichment analysis and protein-protein interaction network construction were performed using bioinformatics methods, revealing miR-223-Abca1 as a crucial miRNA-mRNA pair in lipid metabolism regulation. BV2 microglia cell lines overexpressing miR-223 were engineered, and immunofluorescence staining, western blot, and other techniques were employed to assess LDs accumulation, relevant targets, and inflammatory factor expression, confirming its role in regulating lipid homeostasis in microglia. RESULTS: Histopathological results of our hemicontusion SCI model confirmed LDs aggregation at the injury epicenter, predominantly within microglia. Our transcriptomic analysis during the subacute phase of SCI in mice implicated ATP-binding cassette transporter A1 (Abca1) as a pivotal gene in lipid homeostasis, cholesterol efflux and microglial activation. Integrative mRNA-miRNA multi-omics analysis highlighted the crucial role of miR-223 in the neuroinflammation process following SCI, potentially through the regulation of lipid metabolism via Abca1. In vitro experiments using BV2 cells overexpressing miR-223 demonstrated that elevated levels of miR-223 enhance ABCA1 expression in myelin debris and LPS-induced BV2 cells. This promotes myelin debris degradation and LDs clearance, and induces a shift toward an anti-inflammatory M2 phenotype. CONCLUSIONS: In summary, our study unveils the critical regulatory role of miR-223 in lipid homeostasis following SCI. The mechanism by which this occurs involves the upregulation of ABCA1 expression, which facilitates LDs clearance and myelin debris degradation, consequently alleviating the lipid burden, and inhibiting inflammatory polarization of microglia. These findings suggest that strategies to enhance miR-223 expression and target ABCA1, thereby augmenting LDs clearance, may emerge as appealing new clinical targets for SCI treatment.

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