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Objective: To observe the clinical effect and safety of fire needle therapy combined with bladder function training on neurogenic bladder (NB) caused by spinal cord injury., Methods: A total of 60 patients with NB caused by spinal cord injury were randomly divided into an observation group and a control group , with 30 cases in each group. On the basis of conventional treatment with western medicine, the bladder function training was adopted in the control group, once a day and for 4 weeks. In the observation group, on the basis of the interventions as the control group, fire needling was operated at bilateral Sanyinjiao (SP 6) and Guanyuan (CV 4) and Zhongji (CV 3), once every two days and for 4 weeks (14 interventions in total). Separately, at the baseline and in 2 and 4 weeks of interventions, the urination conditions (average daily urination frequency, average daily leakage frequency, average daily single urination volume) were recorded in the two groups; the urodynamic parameters (maximum flow rate [Qmax], maximum detrusor pressure at maximum flow rate [PdetQmax], residual urine volume [RUA], maximum cystometric capacity [MCC], and bladder pressure) were detected; the neurogenic bladder symptom score (NBSS), urinary symptom distress score (USDS) were observed. Before and after treatment, the score of World Health Organization quality of life assessment scale-brief (WHOQOL-BREF) was observed in the two groups. The therapeutic effect, the incidence of urinary infection, and the safety were evaluated., Results: In 2 and 4 weeks of interventions, the average daily urination frequency, the average daily leakage frequency, RUA, and the scores of NBSS and USDS decreased in the two groups when compared with the baseline ( P <0.05). In 4 weeks of interventions, the above-mention outcomes were lower than those in 2 weeks of interventions ( P <0.05); and the results in the observation group were lower in 2 and 4 weeks of interventions when compared with the control group ( P <0.05). In 2 and 4 weeks of interventions, the average daily single urination volume, Qmax, PdetQmax, MCC, and bladder pressure increased in the two groups compared with the baseline ( P <0.05). In 4 weeks of interventions, the above-mention outcomes were elevated in comparison with those in 2 weeks of interventions ( P <0.05); and except for bladder pressure, the results in the observation group in 2 and 4 weeks of interventions were higher when compared with the control group ( P <0.05). In 4 weeks of interventions, the scores of each dimension and the total scores of WHOQOL-BREF increased in comparison with the baseline in the two groups ( P <0.05), and the scores of the observation group were higher than those of the control group ( P <0.05). The incidence of urinary infection was 0% (0/30) in the observation group and 10.0% (3/30) in the control group, without significant difference ( P >0.05). The total effective rate of the observation group was 93.3% (28/30), which was higher than that (73.3%, 22/30) of the control group ( P <0.05). No serious adverse reactions occurred in the patients of the observation group., Conclusion: Fire needle therapy combined with bladder function training can effectively relieve the clinical symptoms, ameliorate urination, restore bladder function and improve the quality of life in the patients with NB caused by spinal cord injury. This therapeutic regimen presents a high safety in practice.

Macrophages are rapidly activated and polarized toward the M1 phenotype after spinal cord injury (SCI), and inhibiting M1-like macrophages has emerged as a promising SCI treatment approach. Metalloregulatory proteins, which sense specific metal ions with high affinity and specificity, play a critical role in immune regulation. Here, we screened various bioactive metal ions associated with metalloregulatory proteins and discovered that Zn 2+ and Mn 2+ effectively suppressed M1 polarization. Based on these findings, mildly alkaline ZnMn-based layered double hydroxides (ZnMn-LDHs) self-assembled from Zn 2+ coordinated with Mn 2+ were developed to inhibit M1-like macrophages. ZnMn-LDHs effectively neutralized the acidic environment and promoted the expression of metalloregulatory proteins, including metallothionein (MT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2), thereby eliciting robust M1-like macrophage inhibition. More importantly, nerve growth factor (NGF) released by macrophages following the regulation by ZnMn-LDHs promoted the elongation and spreading of Schwann cells. By integrating ZnMn-LDHs with silk fibroin (SF), ZnMn@SF injectable hydrogels were constructed for SCI repair. An in vivo animal model further revealed the excellent anti-inflammatory effects of the ZnMn@SF hydrogels in treating SCI, which promoted functional recovery. Our findings underscore the importance of metalloregulatory proteins regulated by metal ions in inhibiting M1-like macrophages, providing a promising therapeutic strategy for SCI treatment.

Background: Stem-cell derived extracellular vesicles (EVs) have shown promise in preclinical spinal cord injury (SCI) models but lack a comprehensive literature review for clinical translation guidance., Methods: This meta-analysis with trial sequential analysis systematically search PubMed, Web of Science, Embase, and Cochrane Library databases. Prespecified inclusion criteria were studies reporting on measurable outcomes relevant to SCI repair. Risk of bias and quality of reporting were assessed. Random-effects meta-analyses and subgroup analyses comparing natural and bio-engineered EVs were performed. The study was registered with PROSPERO (CRD42024512122)., Findings: The search identified 3935 records, of which 39 studies were included, totaling 1801 animals. Administration of EVs significantly improved locomotor function as measured by Basso-Beattie-Bresnahan or Basso-Mouse-Scale scores at 1 week (natural EVs: SMD 1.50, 95 % CI 1.06-1.95; bio-engineered EVs: SMD 1.93, 95 % CI 1.34-2.52) and 3 weeks (natural EVs: SMD 2.57, 95 % CI 1.96-3.17; bio-engineered EVs: SMD 3.16, 95 % CI 2.29-4.02) post-injury. Subgroup analyses indicated surface modification approaches were most effective among bio-engineered EV strategies. EVs also promoted nerve growth (SMD 2.95, 95 % CI 2.12-3.78), enhanced neuron conductivity (MD 0.75, 95 %CI 0.59-0.90), alleviated inflammation (SMD -3.12, 95 % CI -4.15--2.10), and reduced lesion size (SMD -2.90, 95 % CI -3.87--1.93)., Conclusions: Both natural and bio-engineered EVs improve functional and pathological outcomes in animal models of SCI. The enhanced benefits observed with bio-engineered EVs, particularly those utilizing surface modification approaches, highlight the importance of continued exploration into bio-engineering techniques to optimize EVs' therapeutic efficacy for SCI repair. Protocol Registration CRD42024512122., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.)

Background: The emergence of induced pluripotent stem cells (iPSCs) offers a promising approach for replacing damaged neurons and glial cells, particularly in spinal cord injuries (SCI). Despite its merits, iPSC differentiation into spinal cord progenitor cells (SCPCs) is variable, necessitating reliable assessment of differentiation and validation of cell quality and safety. Phenotyping is often performed via label-based methods including immunofluorescent staining or flow cytometry analysis. These approaches are often expensive, laborious, time-consuming, destructive, and severely limits their use in large scale cell therapy manufacturing settings. On the other hand, cellular biophysical properties have demonstrated a strong correlation to cell state, quality and functionality and can be measured with ingenious label-free technologies in a rapid and non-destructive manner., Method: In this study, we report the use of Magnetic Resonance Relaxometry (MRR), a rapid and label-free method that indicates iron levels based on its readout (T 2 ). Briefly, we differentiated human iPSCs into SCPCs and compared key iPSC and SCPC cellular markers to their intracellular iron content (Fe 3+ ) at different stages of the differentiation process., Results: With MRR, we found that intracellular iron of iPSCs and SCPCs were distinctively different allowing us to accurately reflect varying levels of residual undifferentiated iPSCs (i.e., OCT4 + cells) in any given population of SCPCs. MRR was also able to predict Day 10 SCPC OCT4 levels from Day 1 undifferentiated iPSC T 2 values and identified poorly differentiated SCPCs with lower T 2 , indicative of lower neural progenitor (SOX1) and stem cell (Nestin) marker expression levels. Lastly, MRR was able to provide predictive indications for the extent of differentiation to Day 28 spinal cord motor neurons (ISL-1/SMI-32) based on the T 2 values of Day 10 SCPCs., Conclusion: MRR measurements of iPSCs and SCPCs has clearly indicated its capabilities to identify and quantify key phenotypes of iPSCs and SCPCs for end-point validation of safety and quality parameters. Thus, our technology provides a rapid label-free method to determine critical quality attributes in iPSC-derived progenies and is ideally suited as a quality control tool in cell therapy manufacturing., Competing Interests: Declarations. Ethics approval and consent to participate: This study utilized deidentified iPSC lines and does not involve animals, clinical experiments, or primary patient-derived human tissues. Derivation of the CLEC23 iPSC line had received prior IRB approval (document no.: IRB-2020-05-026, date of approval: 02/06/2020, name of institution: NTU). BJ-iPSCs were derived from the BJ (ATCC CRL-2522) cell line obtained from ATCC ( https://www.atcc.org/products/crl-2522 ) and does not require approvals for derivation as it does not involve the use of patient-derived material. NTU-IRB waived the need for ethical approvals regarding this study in accordance with relevant guidelines and regulations following the Singapore’s Human Tissue Framework under the Human Biomedical Research Act. In accordance to Singapore’s Human Tissue Framework, any form of human biological material which has been substantially manipulated and de-identified are no longer considered human material, and, therefore, ethical approvals or consent to participate does not apply. Consent for publication: Not applicable. Competing interests: J.H., S.Y.C., D.N.R, J.T. filed an intellectual property with a patent that is co-owned by SMART Singapore-MIT Alliance for Research and Technology and NTU. The other authors declared no potential conflicts of interest., (© 2024. The Author(s).)

The repair of traumatic spinal cord injury (SCI) remains a challenge due to the non-regenerative nature of functional neurons in adults. Neural stem cell (NSC)-based therapy has emerged as a promising approach for the treatment of SCI by replacing the damaged neurons with differentiated stem cells. However, directing the neuronal differentiation of implanted stem cells in the injury microenvironment is of great difficulty, especially considering that SCI is generally associated with severe fibrotic tissue infiltration, neuron inflammation, and tissue adhesion. Here, we propose a dual functional Janus film capable of preventing tissue adhesion and promoting the neuronal differentiation of stem cells for the treatment of SCI. The Janus film is composed of a layer of polylactic acid (PLA) and a layer of chitosan (CS) grafted with IKVAV peptides. The PLA layer prevents the invasion of the fibrotic tissue, while the IKVAV peptide-grafted CS layer offers support for NSC implantation and thus the neuronal differentiation of the NSCs. When serving as the dura patch, the Janus films seeded with NSCs promote the recovery of motor function and the regeneration of the injured spinal cord tissue of SCI rats. This dual functional Janus film holds great promise for treating SCI in combination with stem cell therapy.

Bone marrow mesenchymal stem cells (BMMSCs) have garnered attention as promising therapeutic modalities for spinal cord injury (SCI) due to their neuroregenerative, anti-apoptotic, and functional recovery-enhancing properties. The central role of microRNAs (miRNAs) in mediating the beneficial outcomes resulting from BMMSCs in SCI has been highlighted in recent studies, suggesting that targeted modulation of specific miRNAs holds potential for augmenting SCI recovery. Our previous investigation implicated miR-202-3p in the reparative processes of injured spinal cords, although the precise mechanistic underpinnings remain elusive. In vivo, BMMSCs were administered to SCI rats, while in vitro, miR-202-3p was transfected into PC-12 cells. Motor capabilities recovery was assessed via Basso-Beattie-Bresnahan (BBB) scores and footprinting tests; the evaluation of neuronal and spinal cord tissue repair was conducted using Nissl staining, TUNEL staining, hematoxylin and eosin (HE) staining, and immunofluorescence; and the impacts of miR-202-3p on cellular autophagy, neuronal apoptosis, and relevant pathways were evaluated using Western blotting, quantitative polymerase chain reaction (qPCR), and transmission electron microscopy (TEM). Functionally, BMMSCs utilized miR-202-3p to improve motor recovery in SCI rats. Histopathologically, they contributed to the repair of damaged spinal cords and the regeneration of nerve axons. At the molecular level, BMMSCs stimulated autophagy and suppressed neuronal apoptosis by regulating the AMPK, MAPK, and PI3K/AKT/mTOR pathway. Collectively, our findings demonstrate that BMMSCs coordinate miR-202-3p to inhibit mTOR activation via the AMPK, MAPK, and PI3K/AKT pathways, thereby promoting TFEB dephosphorylation, modulating autophagy and neuronal apoptosis, and ultimately fostering functional recovery post-SCI., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All procedures in this study were performed in accordance with the international ethical statutes and law for the protection of animals and were approved by the Animal Research Committee of the First Affiliated Hospital of Nanchang University (Approval No. CDYFY-IACUC 202211 QR 007; Approval Date: 14 November 2022). This study was carried out in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the First Affiliated Hospital of Nanchang University. All methods are reported following ARRIVE guidelines ( https://arriftguidelines.org ) for the reporting of animal experiments., (© 2024. The Author(s).)

Background: In recent years, the utilization of stem cell therapy and cell sheet technology has emerged as a promising approach for addressing spinal cord injury (SCI). However, the most appropriate cell type and mechanism of action remain unclear at this time. This study sought to develop an SCI rat model and evaluate the therapeutic effects of human umbilical cord mesenchymal stem cell (hUC-MSC) sheets in this model. Furthermore, the mechanisms underlying the vascular repair effect of hUC-MSC sheets following SCI were investigated., Methods: A temperature-responsive cell culture method was employed for the preparation of hUC-MSC sheets. The extracellular matrix (ECM) produced by hUC-MSCs serves two distinct yet interrelated purposes. Firstly, it acts as a biologically active scaffold for transplanted cells, facilitating their attachment and proliferation. Secondly, it provides mechanical support and bridges spinal cord stumps, thereby facilitating the restoration of spinal cord function. The formation of the cavity within the spinal cord was evaluated using the Hematoxylin and Eosin (H&E) staining method. Subsequently, endothelial cells were cultivated with the conditioned medium (CM) obtained from hUC-MSCs or hUC-MSC sheets. The pro-angiogenic impact of the conditioned medium of hUC-MSCs (MSC-CM) and the conditioned medium of hUC-MSC sheets (CS-CM) was evaluated through the utilization of the CCK-8 assay, endothelial wound healing assay, and tube formation assay in an in vitro context. The development of glial scars, blood vessels, neurons, and axons in hUC-MSCs and hUC-MSC sheets was assessed through immunofluorescence staining., Results: In comparison to hUC-MSCs, hUC-MSC sheets demonstrated a more pronounced capacity to facilitate vascular formation and induce the regeneration of newborn neurons at the SCI site, while also reducing glial scar formation and significantly enhancing motor function in SCI rats. Notably, under identical conditions, the formation of cell sheets has been associated with a paracrine increase in the ability of the cells themselves to secrete pro-angiogenic growth factors. During the course of the experiment, it was observed that the secretion of uPAR was the most pronounced among the pro-angiogenic factors present in MSC-CM and CS-CM. This finding was subsequently corroborated in subsequent experiments, wherein uPAR was demonstrated to promote angiogenesis via the PI3K/Akt signaling pathway., Conclusion: The creation of cell sheets not only significantly enhances the biological function of hUC-MSCs but also effectively retains the cells locally in spinal cord injury. Therefore, the transplantation of hUC-MSC sheets can maximize the function of hUC-MSCs, greatly reducing glial scar formation, enhancing vascular formation, and promoting the regeneration of neurons and axons. Additionally, the research findings prove that hUC-MSC sheets activate the PI3K/Akt signaling pathway through uPAR secretion to enhance angiogenesis. The transfer of the entire extracellular matrix by hUC-MSC sheets, in the absence of the introduction of additional exogenous or synthetic biomaterials, serves to further augment their potential for clinical application., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: Spinal cord injury (SCI) can result in sensory and locomotor function loss below the injured segment. Hyperbaric oxygen therapy (HBOT) has been proven to alleviate SCI. This study aims to establish a reproducible rat model of SCI and investigate the impact of HBOT on alterations in brain neuronal activity and neuromotor function in this experimental rat SCI model using resting-state functional magnetic resonance imaging (rs-fMRI)., Methods: This is a prospective randomized controlled animal trial. A total number of 27 female SD rats were randomly divided into three groups: sham (n = 9), SCI (n = 9), and HBO (n = 9). rs-fMRI was utilized to assess regional homogeneity (ReHo) values and functional connectivity (FC) strength over the whole brain with the motor cortex as seeds. Correlation between neuroimaging characteristics and behavioral assessment was calculated. We examined Nissl body, NeuN, and caspase-3 expression in relevant brain regions., Results: Following SCI, reduced ReHo values were observed in the left primary somatosensory cortex, left striatum, right agranular insular cortex, and partial cortex in the limbic system, which was reversed after HBOT. HBOT could increase FC strength between the motor cortex and other brain regions, including the left secondary motor cortex, right basal forebrain region, bilateral primary somatosensory cortex, bilateral thalamus, and another partial cortex in the limbic system. BBB scale scores showed that HBOT promoted motor function recovery in SCI rats. The ReHo and FC values in all positive clusters were positively correlated with BBB scores. By histopathological analysis, our study found that HBOT could reduce apoptotic proteins, increase the number of neurons, and protect neuronal function in brain regions with significant ReHo and FC alteration in SCI rats., Conclusion: This study reveals that HBOT facilitates functional and structural plasticity in the brain, contributing to the recovery of motor function in rats with SCI., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Introduction: Spinal cord injury (SCI) is a devastating condition that can lead to permanent neurological deficits. Stem cell transplantation is a promising therapeutic approach for promoting spinal cord repair and functional recovery. However, assessing the extent of repair and regeneration remains a challenge. Diffusion tensor imaging (DTI) has been proposed as a non-invasive imaging technique to evaluate the microstructural integrity of the spinal cord following stem cell transplantation. This systematic review aimed to evaluate the utility of DTI in assessing spinal cord repair following stem cell transplantation in SCI., Search Strategy: We conducted a comprehensive literature search in multiple electronic databases (PubMed, Embase, Web of Science, and Cochrane Library) to identify relevant studies that utilized DTI to evaluate spinal cord repair after stem cell transplantation in animal models or clinical trials of SCI. The search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven relevant articles were identified and included in the review., Results: Of the seven studies, five were preclinical animal studies, and two were clinical trials. Across the studies, 142 subjects (112 animals and 30 human patients) underwent DTI evaluation after stem cell transplantation. Meta-analysis revealed a significant increase in fractional anisotropy(FA; mean difference = 0.12; 95% CI: 0.08-0.16; p = 0.001) and a significant decrease in mean diffusivity (MD) (mean difference = -0.15 × 10-3 mm2/s; 95% CI: -0.21 to -0.09; p= 0.001) in the transplanted regions compared to control groups. These DTI changes correlated with improved functional outcomes and histological evidence of axonal regeneration and remyelination., Conclusion and Discussion: DTI is a valuable non-invasive imaging technique for evaluating spinal cord microstructural changes following stem cell transplantation in SCI. Increased FA and decreased MD suggest improved axonal integrity and myelination, corresponding with functional recovery and histological repair. DTI can provide insights into stem cell-mediated repair mechanisms and guide therapeutic decision-making.

A spinal cord injury (SCI) disrupts the neuronal projections from the brain to the region of the spinal cord that produces walking, leading to various degrees of paralysis. Here, we aimed to identify brain regions that steer the recovery of walking after incomplete SCI and that could be targeted to augment this recovery. To uncover these regions, we constructed a space-time brain-wide atlas of transcriptionally active and spinal cord-projecting neurons underlying the recovery of walking after incomplete SCI. Unexpectedly, interrogation of this atlas nominated the lateral hypothalamus (LH). We demonstrate that glutamatergic neurons located in the LH (LH Vglut2 ) contribute to the recovery of walking after incomplete SCI and that augmenting their activity improves walking. We translated this discovery into a deep brain stimulation therapy of the LH (DBS LH ) that immediately augmented walking in mice and rats with SCI and durably increased recovery through the reorganization of residual lumbar-terminating projections from brainstem neurons. A pilot clinical study showed that DBS LH immediately improved walking in two participants with incomplete SCI and, in conjunction with rehabilitation, mediated functional recovery that persisted when DBS LH was turned off. There were no serious adverse events related to DBS LH . These results highlight the potential of targeting specific brain regions to maximize the engagement of spinal cord-projecting neurons in the recovery of neurological functions after SCI. Further trials must establish the safety and efficacy profile of DBS LH , including potential changes in body weight, psychological status, hormonal profiles and autonomic functions., Competing Interests: Competing interests: G.C., J.B., N.C., J.W.S., R.D., L.A. and L.B.-F. hold various patents in relation to the present work. G.C. is a consultant of ONWARD Medical. G.C. and J.B. are minority shareholders of ONWARD Medical, a company with partial relationships with the presented work. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Spinal cord injury (SCI) is a devastating injury that significantly impairs patients' quality of life. To date, there is no effective treatment to mitigate nerve tissue damage and restore neurological function. Neural stem cells (NSCs) derived from human embryonic stem cells (hESCs) are considered an important cell source for reconstructing damaged neural circuits and enabling axonal regeneration. Recent preclinical studies have shown that NSCs are potential therapeutic cell sources for neuroprotection and neuroregeneration in SCI animal models. NSCs can be derived from different sources and the spinal cord-specific NSCs have a higher potential for the regeneration of SCI. However, the long-term therapeutic efficacy of spinal cord-specific NSCs remains unproven. Here, we generated human spinal cord NSCs (hSCNSCs) and investigated the effects of transplanted hSCNSCs on the repair of the SCI model rats for 60 days. The transplanted hSCNSCs improved BBB scores, reduced the lesion area and promoted an increase in the number of Nestin-positive cells in the spinal cord compared to the model rats. Meanwhile, hSCNSC transplantation promoted the expression of synaptophysin, a synaptic signature protein and MBP, a protein associated with remyelination. Interestingly, BAF45D, a chromatin remodelling factor that contributes to the induction of hSCNSCs with region-specific spinal cord identity, were increased by the hSCNSC transplantation. In addition, conditioned medium derived from the hSCNSCs also promoted regenerative repair of the injured spinal cord. These results demonstrate that hSCNSCs may play a critical role in the regenerative repair of SCI., (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Spinal cord injury (SCI) leads to significant bone loss resulting in osteoporosis and an increased risk of fractures below the level of injury. It is imperative to screen for osteoporosis in all individuals with SCI starting immediately after the acute injury. Although data are limited, clinicians are encouraged to discuss preventative treatment in the acute SCI period and to treat osteoporosis when diagnosed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The incidence of nerve tissue injuries, such as peripheral nerve injury, spinal cord injury, traumatic brain injury, and various neurodegenerative diseases (NDs), is continuously increasing because of stress, physical and chemical trauma, and the aging population worldwide. Restoration of the damaged nervous system is challenging because of its structural and functional complexity and limited regenerative ability. Additionally, there is no cure available for NDs except for medications that provide symptomatic relief. Stem cells offer an alternative approach for promoting damage repair, but their efficacy is limited by a compromised survival rate and neurogenesis process. To address these challenges, neural tissue engineering has emerged as a promising strategy in which stem cells are seeded or encapsulated within a suitable biomaterial construct, increasing cell survival and neurogenesis. Numerous biomaterials are utilized to create different types of constructs for this purpose. Researchers are trying to develop ideal scaffolds that combine biomaterials, cells, and molecules that exactly mimic the biological and mechanical properties of the tissue to achieve functional recovery associated with neurological dysfunction. This review focuses on exploring the development and applications of different biomaterials for their potential use in the diagnosis, therapy, nerve tissue regeneration, and treatment of neurological disorders., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Spinal cord injury (SCI) damages the trauma site, leading to progressive and secondary structural defects rostral and caudal to the injury. Interruption of ascending and descending pathways produce motor, sensory, and autonomic impairments, driving the need for effective therapies. In this study, we address lesion site repair and promoting descending projections using a combined biomaterial-neuromodulation strategy in a rat model of cervical contusion SCI. To promote tissue repair, we used Chitosan fragmented physical hydrogel suspension (C fphs ), a biomaterial formulation optimized to mitigate inflammation and support tissue remodeling. To promote descending projections, we targeted the corticospinal motor system with dual motor cortex-trans-spinal direct current neuromodulation to promote spared corticospinal tract (CST) axon sprouting rostral and caudal to SCI. C fphs , injected into the lesion site acutely, was followed by 10 days of daily neuromodulation. Analysis was made at the chronic phase, 8-weeks post-SCI. Compared with SCI only, C fphs alone or in combination with neuromodulation prevented cavity formation, by promoting tissue remodeling at the injury site, abrogated astrogliosis surrounding the newly formed tissue, and enabled limited CST axon growth into the remodeled injury site. C fphs alone significantly reduced CST axon dieback and was accompanied by preserving more CST axon gray matter projections rostral to SCI. C fphs  + neuromodulation produced sprouting rostral and caudal to injury. Our findings show that our novel biomaterial-neuromodulation combinatorial strategy achieves significant injury site tissue remodeling and promoted CST projections rostral and caudal to SCI., Competing Interests: Declaration of competing interest Drs. Fatiha Nothias and Sylvia Soares are co-founders and stock owners of MEDJEDUSE and co-owners of the patent for which MEDJEDUSE owns an exclusive commercial sublicence. They declare no competing financial interests. Ms. Chaimae Ahmanna and Ms. Kadia Kanté were employees of Medjeduse when the work was conducted. The biomaterial being evaluated in this article is provided by MEDJEDUSE., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Study Design: Guided by the 4-step process outlined in the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) guideline, multiple methodologies were used: Delphi, literature reviews, ratings with consensus, think-aloud, and test-retest., Objectives: The purpose of this study was to develop and test a spinal cord injury (SCI) peer support evaluation tool that meets the needs of community-based SCI organizations in Canada., Setting: Peer support programs for people with SCI delivered by community-based SCI organizations., Methods: This research was co-constructed with executives and staff from SCI community-based organizations, people with SCI, researchers, and students. Given the multiple steps of this study, sample size and characteristics varied based on each step. Participants included people with SCI who received peer support (mentees) or provided peer support (mentors/supporters) and staff of community-based organizations., Results: In step 1, the 20 most important outcomes for SCI peer support were identified. In step 2 and 3, the 97 items were identified to assess the outcomes and by using rating and multiple consensus methodologies 20 items, one to assess each outcome, were selected. In step 4, content and face validity and test-retest reliability were achieved. The resulting SCI Peer Support Evaluation Tool consists of 20 single-item questions to assess 20 outcomes of SCI peer support., Conclusion: Through a systematic process, the SCI Peer Support Evaluation Tool is now ready to be implemented to assess outcomes of SCI peer support programs delivered by community-based SCI organizations., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research. Ethics approval for this study was obtained from the McGill University Research Ethics Board (REB#: 21-11-011)., (© 2024. The Author(s).)

A severe disorder known as spinal cord damage causes both motor and sensory impairment in the limbs, significantly reducing the patients' quality of life. After a spinal cord injury, functional recovery and therapy have emerged as critical concerns. Hydrogel microspheres have garnered a lot of interest lately because of their enormous promise in the field of spinal cord injury rehabilitation. The material classification of hydrogel microspheres (natural and synthetic macromolecule polymers) and their synthesis methods are examined in this work. This work also covers the introduction of several kinds of hydrogel microspheres and their use as carriers in the realm of treating spinal cord injuries. Lastly, the study reviews the future prospects for hydrogel microspheres and highlights their limitations and problems. This paper can offer feasible ideas for researchers to advance the application of hydrogel microspheres in the field of spinal cord injury., (© 2024 Wiley Periodicals LLC.)

Background: Consequences of spinal cord injury (SCI) with a sedentary lifestyle will progress to muscle weakness and muscle atrophy, leading to muscle fatigue. This study aimed to determine the feasibility and preliminary effects of high-intensity interval training (HIIT) using functional electrical stimulation (FES) cycling on changes in thigh muscle volume and muscle strength, in patients with incomplete SCI., Methods: Eight incomplete SCI patients (mean age 50 years; 6 women) with stable SCI paraplegia (mean 6.75 years since injury) participated in the HIIT FES cycling (85%-90% peak Watts; 4 × 4-min intervals) three times a week (over 6 weeks). The main outcomes were adherence, participant acceptability, and adverse events. Secondary outcomes were muscle strength (peak torque) and leg volume changes., Results: Our findings revealed that the program was well-received by participants, with high levels of adherence, positive feedback, and satisfaction, suggesting that it could be a promising option for individuals seeking to enhance their lower body strength and muscle mass. Additionally, all participants successfully completed the training without any serious adverse events, indicating that the program is safe for use. Finally, we found that the 6-week HIIT FES leg cycling exercise program resulted in notable improvements in isometric peak torque of the quadriceps (range 13.9%-25.6%), hamstring muscle (18.2%-23.3%), and leg volume (1.7%-18.2%)., Conclusions: This study highlights HIIT FES leg cycling exercise program potential as an effective intervention for improving lower limb muscle function., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Spinal cord injury (SCI) often leads to neurological dysfunction, and neuronal cell death is one of the main causes of neurological dysfunction. After SCI, in addition to necrosis, programmed cell death (PCD) occurs in nerve cells. At first, studies recognized only necrosis, apoptosis, and autophagy. In recent years, researchers have identified new forms of PCD, including pyroptosis, necroptosis, ferroptosis, and cuproptosis. Related studies have confirmed that all of these cell death modes are involved in various phases of SCI and affect the direction of the disease through different mechanisms and pathways. Furthermore, regulating neuronal cell death after SCI through various means has been proven to be beneficial for the recovery of neural function. In recent years, emerging therapies for SCI have also provided new potential methods to restore neural function. Thus, the relationship between SCI and cell death plays an important role in the occurrence and development of SCI. This review summarizes and generalizes the relevant research results on neuronal necrosis, apoptosis, autophagy, pyroptosis, necroptosis, ferroptosis, and cuproptosis after SCI to provide a new understanding of neuronal cell death after SCI and to aid in the treatment of SCI., Competing Interests: Declarations. Ethics Approval and Consent to Participate: Not applicable. Consent to Participate: Not applicable. Consent for Publication: Not applicable. Conflicts of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Spinal cord injury (SCI) is a severe lesion comporting various motor, sensory and sphincter dysfunctions, abnormal muscle tone and pathological reflex, resulting in a severe and permanent lifetime disability. The primary injury is the immediate effect of trauma and includes compression, contusion, and shear injury to the spinal cord. A secondary and progressive injury usually follows, beginning within minutes and evolving over several hours after the first ones. Because ischemia is one of the most important mechanisms involved in secondary injury, a treatment to increase the oxygen tension of the injured site, such as hyperbaric oxygen therapy, should theoretically help recovery. Although a meta-analysis concluded that hyperbaric oxygen therapy might be helpful for clinical treatment as a safe, promising and effective choice to limit secondary injury when appropriately started, useful and well-defined protocols/guidelines still need to be created, and its application is influenced by local/national practice. The topic is not a secondary issue because a well-designed randomized controlled trial requires a proper sample size to demonstrate the clinical efficacy of a treatment, and the absence of a common practice guideline represents a limit for results generalization. This narrative review aims to reassemble the evidence on hyperbaric oxygen therapy to treat SCI, focusing on adopted protocols in the studies and underlining the critical issues. Furthermore, we tried to elaborate on a protocol with a flowchart for an evidence-based hyperbaric oxygen therapy treatment. In conclusion, a rationale and shared protocol to standardize as much as possible is needed for the population to be studied, the treatment to be adopted, and the outcomes to be evaluated. Further studies, above all, well-designed randomized controlled trials, are needed to clarify the role of hyperbaric oxygen therapy as a strategic tool to prevent/reduce secondary injury in SCI and evaluate its effectiveness based on an evidence-based treatment protocol. We hope that adopting the proposed protocol can reduce the risk of bias and drive future studies., (Copyright © 2023 Chinese Medical Association. Published by Elsevier B.V. All rights reserved.)

Spinal cord injury (SCI) is a severe neurological condition that can lead to paralysis or even death. This study explored the potential benefits of bone marrow mesenchymal stem cell (BMSC) transplantation for repairing SCI. BMSCs also differentiate into astrocytes within damaged spinal cord tissues hindering the cell transplantation efficacy, therefore it is crucial to enhance their neuronal differentiation rate to facilitate spinal cord repair. Wnt5a, an upstream protein in the non-classical Wnt signaling pathway, has been implicated in stem cell migration, differentiation, and neurite formation but its role in the neuronal differentiation of BMSCs remains unclear. Thus, this study investigated the role and underlying mechanisms of Wnt5a in promoting neuronal differentiation of BMSCs both in vivo and in vitro. Wnt5a enhanced neuronal differentiation of BMSCs in vitro while reducing astrocyte differentiation. Additionally, high-throughput RNA sequencing revealed a correlation between Wnt5a and phosphoinositide 3-kinase (PI3K)/protein kinase B(AKT) signaling, which was confirmed by the use of the PI3K inhibitor LY294002 to reverse the effects of Wnt5a on BMSC neuronal differentiation. Furthermore, transplantation of Wnt5a-modified BMSCs into SCI rats effectively improved the histomorphology (Hematoxylin and eosin [H&E], Nissl and Luxol Fast Blue [LFB] staining), motor function scores (Footprint test and Basso-Beattie-Bresnahan [BBB]scores)and promoted neuron production, axonal formation, and remodeling of myelin sheaths (microtubule associated protein-2 [MAP-2], growth-associated protein 43 [GAP43], myelin basic protein [MBP]), while reducing astrocyte production (glial fibrillary acidic protein [GFAP]). Therefore, targeting the Wnt5a/PI3K/AKT pathway could enhance BMSC transplantation for SCI treatment., Competing Interests: Declarations. Ethics Approval: The animal experiment was complied with the Compilation of Group Standards and Implementation Guidelines of the Chinese Society for Laboratory Animals (CSLA). The animal care procedures were reviewed and approved by the Animal Ethics Committee of Guangzhou University of Chinese Medicine (approval number: 20220803007). Consent for Publication: We obtained permissions from the participants to publish their data. All participants gave written consent for publication. Competing Interests: The authors declare no competing interests., (© 2024. The Author(s).)

The prevalence of closed-system central nervous system (CNS) injuries underscores the need for an enhanced understanding of these traumas to improve protective and therapeutic interventions. Crucial to this research are animal models that replicate closed-system CNS injuries. In this context, a custom overpressure air system was engineered to reproduce a range of closed-system CNS injuries in murine models, including ocular, brain, and spinal cord trauma. To date, the system has been used to administer eye-, head-, or spine-directed overpressure air to model anteroposterior pole injury in the eye, indirect traumatic optic neuropathy (ITON), focal traumatic brain injury, and spinal cord injury. This paper provides a detailed protocol outlining the system's design and operation and shares representative results demonstrating its effectiveness. The robust framework presented here provides a strong foundation for ongoing research in CNS trauma. By leveraging the system's flexible attributes, investigators can modify and carefully control the location, severity, and timing of injuries. This allows for comprehensive comparisons of molecular mechanisms and therapeutic efficacy across multiple closed-system CNS injuries.

Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of H 2 O 2 -treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage., Competing Interests: Declarations. Competing interest: The authors declare no competing interests. Ethical approval: The present study was approved by the Animal experiments were approved by Wuxi No.8 People’s Hospital Animal Experimental Ethics Committee (Approval number: 2015JN7211). and all procedures complied with the National Institutes of Health Guide for the Use of Laboratory Animals., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Spinal cord injury (SCI) involves a continuous and dynamic cascade of complex reactions, with mitochondrial damage and dysfunction-induced energy metabolism disorders playing a central role throughout the process. These disorders not only determine the severity of secondary injuries but also influence the potential for axonal regeneration. Given the critical role of energy metabolism disturbances in the pathology of SCI, strategies such as enhancing mitochondrial transport within axons to alleviate local energy deficits, or transplanting autologous or allogeneic mitochondria to restore energy supply to damaged tissues, have emerged as potential approaches for SCI repair. These strategies also aim to modulate local inflammatory responses and apoptosis. Preclinical studies have initially demonstrated that mitochondrial transplantation (MT) significantly reduces neuronal death and promotes axonal regeneration following spinal cord injury. MT achieves this by regulating signaling pathways such as MAPK/ERK and PI3K/Akt, promoting the expression of growth-associated protein-43 (GAP-43) in neurons, and inhibiting the expression of apoptosis-related proteins like Grp78, Chop, and P-Akt, thereby enhancing the survival and regeneration of damaged neurons. Additionally, MT plays a role in promoting the expression of vascular endothelial growth factor, facilitating tissue repair, and reducing the secretion of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6. Furthermore, MT modulates neuronal apoptosis and inflammatory responses by decreasing the expression of p-JNK, a member of the MAPK family. In summary, by reviewing the detailed mechanisms underlying the cascade of pathological processes in SCI, we emphasize the changes in endogenous mitochondria post-SCI and the potential of exogenous MT in SCI repair. This review aims to provide insights and a basis for developing more effective clinical treatments for SCI., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: All authors confirm their consent for publication. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Even though people with spinal cord injury are usually followed by a spinal cord injury specialist, studies show that they continue to be monitored by their general practitioner. In Switzerland, over a one-year period, 88 % of spinal cord injury patients consult their general practitioner. The five most common health problems reported by people with spinal cord injury are pain, spasticity, neurogenic disorders of bladder and bowel function, and urinary tract infections. Even if these are common problems in primary care medicine, it is important for general practitioner to be aware of the specificities of spinal cord injury patients, to ensure optimal management. This article provides some useful information on the management of spinal cord injured patients in outpatient care., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Due to the uncertain differentiation of neural stem cells (NSCs), replenishing lost neurons by endogenous neural differentiation to repair spinal cord injury (SCI) remains challenging. The electrical stimulation-induced drug release is a promising approach for the localized and controlled release of drugs to regulate the differentiation of NSCs into neurons. Here, we developed Zn-PDA@BT nanoparticles acted as Trojan Horse to enter cells through endocytosis for Zn 2+ -controlled release therapy by the potentials generated by the piezoelectric effect. Due to the presence of polydopamine (PDA), under ultrasound stimulation, the electrical signal derived from the piezoelectric effect of barium titanate nanoparticles can be attracted to the surface of Trojan Horse nanoparticles to facilitate the controlled release of Zn 2+ . And Zn 2+ bonded with PDA can increase the intracellular Zn 2+ concentration within mouse-derived NSCs (mNSCs) to regulate the differentiation of mNSCs, which could enhance excitatory neuronal differentiation and inhibit astrocyte differentiation of mNSCs by activating the TGF-β and p53 pathways. More importantly, this Trojan Horse therapy allowed mNSCs to differentiate into mature neurons in 5 days, while the natural differentiation process took 10 days. Moreover, the transplantation of mNSC-ingested Zn-PDA@BT nanoparticles effectively replenished lost neurons at the damaged site and promoted function recovery after SCI in vivo, demonstrating the great potential of electrical stimulation-induced Zn 2+ release for SCI repair.

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B2) on expression of high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) related proteins and inflammation-related factors in spinal cord injury (SCI) rats, so as to explore the dynamic process of inhibiting inflammatory response in rats with SCI, and to provide a new idea and theoretical basis of molecular biology for the treatment of SCI., Methods: Fifty-four SD rats were randomly divided into sham operation, model, and EA groups ( n =18 in each group), which were further divided into 3 d, 7 d and 14 d subgroups, with 6 rats at each time point. The SCI model was established according to the Allen's method. Rats in EA group received EA (1 mA, 100 Hz) intervention at EX-B2 of T9 and T11 24 hours after modeling for 30 min, once a day for 3 d, 7 d, or 14 d, respectively. The motor function of rats' hind limbs was evaluated using BBB scale, the morphological structure of rats' spinal cord tissue was observed by H.E. staining. The contents of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in spinal cord tissue were detected by ELISA. Western blot and immunofluorescence staining were used to detect the relative protein expression and fluorescence positive expression of HMGB1, TLR4 and NF-κB p65 in spinal cord tissue, respectively., Results: Compared with the sham operation group, the BBB scores after modeling and on day 3, 7 and 14 were all decreased ( P <0.05), while the contents of iNOS and COX-2 in spinal cord tissue, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were increased ( P <0.05) in the model group. In comparison with the model group, the BBB scores on day 3, 7 and 14 were obviously increased ( P <0.05), while the contents of iNOS and COX-2, the protein expression and fluorescence positive expression of HMGB1, TLR4, and NF-κB p65 were significantly down-regulated in the EA group ( P <0.05)., Conclusions: EA of "Jiaji" can promote the recovery of SCI neurological function, which may be related to its function in regulating the HMGB1/TLR4/NF-κB signaling pathway, down-regulating the expression of iNOS and COX-2, and inhibiting the neuroinflammatory response after SCI.

Objectives: To observe the effect of electroacupuncture (EA) stimulation of "Dazhui"(GV14) and "Mingmen" (GV4) of the Governor Vessel (GV) on the apoptosis of neurons in rats with spinal cord injury (SCI) by regulating the expression of glycogen synthase kinase-3β (GSK-3β) protein and its phosphorylation level, so as to reveal partial mechanism for the treatment of SCI with EA of GV., Methods: A total of 45 male SD rats were randomly divided into sham-operation, model and EA groups, 15 rats in each group. The SCI model was established by using the modified Allen's percussion device. EA stimulation (2 Hz, 1 mA) was applied to GV14 and GV4 for 20 min, once daily for 28 days. Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to assess the rat's hind limb motor function at the 1 st , 7 th , 14 th , 21 th and 28 th day after modeling. H.E. staining was used to observe the histopathological changes of the injured spinal cord tissue. The expressions of GSK-3β and its phosphorylation at Ser9 site in the spinal cord were detected by immunohistochemistry and Western blot, respectively. The TUNEL staining was used to observe the apoptosis of neuron in the spinal cord., Results: In comparison with the control group, the BBB scores from day 1 to day 28, and the expression and immunoactivity of p-GSK-3β were significantly decreased ( P <0.01), while the expression and immunoactivity of GSK-3β and the apoptosis index were significantly increased ( P <0.01) in the model group. In contrast to the model group, the EA group had a remarkable increase in the BBB score from day 7 to day 28, and the expression and immunoactivity of p-GSK-3β ( P <0.05, P <0.01), and an obvious decrease ( P <0.05, P <0.01) in the expression and immunoactivity of GSK-3β and the apoptosis index. H.E. staining showed that in the model group, the spinal cord structure of the SCI region was disorganized, with tissue cavity, blurred gray matter boundary, severe inflammatory infiltration, reduction of normal neurons, loss of cytoplasm, and nuclear contraction, which was relatively milder in the EA group., Conclusions: EA at GV14 and GV4 can improve the symptoms of neurological function injury and reduce the apoptosis of neurons in rats with SCI, which may be achieved by regulating GSK-3β protein and its phosphorylation level.

Improved treatment options are urgently needed for neurological injuries resulting from trauma or iatrogenic events causing long-term disabilities that severely impact patients' quality of life. In vitro and animal studies have provided promising proof-of-concept examples of regenerative therapies using mesenchymal stromal cells (MSC) for a wide range of pathological conditions. Over the previous decade, various MSC-based therapies have been investigated in clinical trials to treat traumatic neurological injuries. However, while the safety and feasibility of MSC treatments has been established, the patient outcomes in these studies have not demonstrated significant success in the translation of MSC regenerative therapy for the treatment of human brain and spinal cord injuries. Herein, we have reviewed the literature and ongoing registered trials on the application of MSC for the treatment of traumatic brain injury, traumatic spinal cord injury, and peripheral nerve injury. We have focused on the shortcomings and technological hurdles that must be overcome to further advance clinical research to phase 3 trials, and we discuss recent advancements that represent potential solutions to these obstacles to progress., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: Xiujuan Wang, Ying Yang and Yongsheng Xu are employees of Tianjin Everunion Biotechnology Co., Ltd. Qian Wang and Jiaxian Wang are employees of HELP Therapeutics Co., Ltd. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Electrical motor cortex stimulation can produce corticospinal system plasticity and enhance motor function after injury. We investigate molecular mechanisms of structural and physiological plasticity following electrical neuromodulation, focusing on identifying molecular predictors, or biomarkers, for durable plasticity. We used two neuromodulation protocols, repetitive multipulse stimulation (rMPS) and patterned intermittent theta burst stimulation (iTBS), incorporating different stimulation durations and follow-up periods. We compared neuromodulation efficacy in promoting corticospinal tract (CST) sprouting, motor cortex muscle evoked potential (MEP) LTP-like plasticity, and their associated molecular underpinnings. Only iTBS produced CST sprouting after short-term neuromodulation (1 d of stimulation; 9-d survival for sprouting expression); both iTBS and rMPS produced sprouting with long-term (10-d) neuromodulation. Significant mTOR signaling activation and phosphatase and tensin homolog (PTEN) protein deactivation predicted axon growth across all neuromodulation conditions that produced significant sprouting. Both neuromodulation protocols, regardless of duration, were effective in producing MEP enhancement. However, persistent LTP-like enhancement of MEPs at 30 d was only produced by long-term iTBS. Statistical modeling suggests that Stat3 signaling is the key mediator of MEP enhancement. Cervical spinal cord injury (SCI) alone did not affect baseline molecular signaling. Whereas iTBS and rMPS after SCI produced strong mTOR activation and PTEN deactivation, only iTBS produced Stat3 activation. Our findings support differential molecular biomarkers for neuromodulation-dependent structural and physiological plasticity and show that motor cortex epidural neuromodulation produces molecular changes in neurons that support axonal growth after SCI. iTBS may be more suitable for repair after SCI because it promotes molecular signaling for both CST growth and MEP plasticity., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aside from enabling voluntary control over paralyzed muscles, a key effect of spinal cord stimulation is the alleviation of spasticity. Dysfunction of spinal inhibitory circuits is considered a major cause of spasticity. These circuits are contacted by Ia muscle spindle afferents, which are also the primary targets of transcutaneous lumbar spinal cord stimulation (TSCS). We hypothesize that TSCS controls spasticity by transiently strengthening spinal inhibitory circuit function through their Ia-mediated activation. We show that 30 min of antispasticity TSCS improves activity in post- and presynaptic inhibitory circuits beyond the intervention in ten individuals with traumatic spinal cord injury to normative levels established in 20 neurologically intact individuals. These changes in circuit function correlate with improvements in muscle hypertonia, spasms, and clonus. Our study opens the black box of the carryover effects of antispasticity TSCS and underpins a causal role of deficient post- and presynaptic inhibitory circuits in spinal spasticity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Dental pulp stem cells (DPSCs) show potential for treating neurodegenerative and traumatic diseases due to their neural crest origin. Melatonin (MT), an endogenous neurohormone with well-documented anti-inflammatory and antioxidant properties, has shown promising results with MSCs in terms of engraftment, proliferation, and neuronal differentiation in animal SCI models. However, the effects of melatonin preconditioning on human dental pulp stem cells (hDPSCs) for SCI treatment remain unclear. This study investigates the impact of melatonin preconditioning on hDPSCs engraftment, neural differentiation, and neurological function in rats with SCI. Forty-two male Sprague-Dawley rats were divided into six groups: Control, Sham, Model, Vehicle, Lesion Treatment A (SCI + hDPSCs), and Lesion Treatment B (SCI + MT-hDPSCs). After obtaining hDPSCs, stem cells were evaluated using flow cytometry. Cell viability was assessed using the MTT assay. SCI was induced in the Model, Vehicle, Lesion Treatment A, and Lesion Treatment B groups. The Lesion Treatment A and B groups received hDPSCs and hDPSCs pretreated with melatonin, respectively, 1 week after SCI, while the Vehicle group received only an intravenous injection of DMEM to simulate treatment. The other groups were used for behavioral testing. Immunohistochemistry (IHC) was employed to assess hDPSCs engraftment and differentiation at the SCI site. Motor function across the six groups was evaluated using the Basso, Beattie, and Bresnahan (BBB) score. Histological studies and cell counts confirmed hDPSCs implantation at the injury site, with a significantly higher presence in the MT-hDPSCs compared to hDPSCs (p < 0.01). IHC revealed that hDPSCs and MT-hDPSCs differentiated into neurons and astrocytes, with greater differentiation observed in the MT-hDPSCs compared to the hDPSCs (p < 0.01 and p < 0.05, respectively). Functional improvement was noted in both SCI + hDPSCs and SCI + MT-hDPSCs groups compared to SCI and Vehicle groups from Week 4 onward (p < 0.001). Significant differences were also observed between the SCI + hDPSCs and SCI + MT-hDPSCs groups starting from Week 7 (p < 0.01). Preconditioning hDPSCs with melatonin enhances engraftment, neuronal differentiation, and greater performance improvement compared to hDPSCs alone in the SCI animal model., Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval and consent to participate The experimental protocols were approved by the Animal Experimentation Ethics Committee of Guilan University of Medical Sciences (IR.GUMS.REC.1400.175) and were conducted in accordance with the animal ethics guidelines of national health and research institutes. This study is reported following ARRIVE guidelines., (© 2024. The Author(s).)

This study aims to investigate the effect of adipose-derived stem cells (ADSCs) transplantation on progranulin (PGRN) expression and functional recovery in rats with spinal cord injury (SCI). ADSCs were isolated from the inguinal adipose tissue of rats. A SCI model was created, and ADSCs were injected into the injured area. Various techniques were used to assess the effects of ADSCs transplantation, including hematoxylin-eosin staining, Masson staining, immunofluorescence staining, electron microscopy, MRI, and motor function assessment. The potential mechanisms of ADSC transplantation were investigated using gene expression analysis and protein analysis. Finally, the safety of this therapy was evaluated through hematoxylin-eosin staining and indicators of liver and kidney damage in serum. PGRN expression increased in the injured spinal cord, and ADSCs transplantation further enhanced PGRN levels. The group that received ADSCs transplantation showed reduced inflammation, decreased scar formation, increased nerve regeneration, and faster recovery of bladder function. Importantly, motor function significantly improved in the ADSC transplantation group. ADSCs transplantation enhances functional regeneration in SCI by upregulating PGRN expression, reducing inflammation and scar formation, and promoting nerve regeneration and myelin repair. These findings suggest that ADSC transplantation is a potential therapy for SCI., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury., (© 2024. The Author(s).)

Spinal cord injury is a serious disease of the central nervous system. The electrophysiological properties of the spinal cord that are essential to maintaining neurotransmission can be impaired after the injury. Therefore, electrophysiological evaluation is becoming an important indicator of the injury extent or the therapeutic outcomes by reflecting the potential propagation of neural pathways. On the other hand, the repair of damaged nerves is one of the main goals of spinal cord injury treatment. Growing research interest has been concentrated on developing effective therapeutic solutions to restore the normal electrophysiological function of the injured spinal cord by using conductive materials and/or exerting the merits of electrical stimulation. Accordingly, this review introduces the current common electrophysiological evaluation in spinal cord injury. Then the cutting-edge therapeutic strategies aiming at electrophysiological improvement in spinal cord injury are summarized. Finally, the challenges and future prospects of neural restoration after spinal cord injury are presented.

Transplanted mesenchymal stem cells (MSCs) can significantly aid in repairing spinal cord injuries (SCIs) 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 toward the SCI site in response to HGF. It was found that HGF can activate β-catenin signaling in MSCs by either phosphorylating LRP6, suppressing GSK3β phosphorylation through the AKT and ERK1/2 pathways, or 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 β-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 β-catenin signaling in MSCs, ultimately triggering their chemotactic migration., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: Declaration of competing interest We confirmed that the paper has been seen and admitted by co-authors, approved the submission to the journal. We confirmed that there are no conflicts of interest in this paper. Thank you very much., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Investigating the role of cranial bone marrow mesenchymal stem cells (cBMMSC) based on nanosilver hydrogel nerve conduits in the repair of spinal cord injury. Thirty adult Wistar rats, male and female, with body mass of 210-240 g, were selected as experimental animals and divided into control group and experimental group, 15 rats each, by random number table method. The experimental group was treated with spinal cord injury and localized transplantation of cBMMSC-containing nanosilver hydrogel nerve conduits, while the control group was treated with spinal cord injury and localized transplantation of cBMMSC-free nanosilver hydrogel nerve conduits. Four weeks after transplantation, the expression of neuron-specific enolase (NSE) in rat anti-human nuclear monoclonal antibody (MAB1281)-positive cells was detected by immunostaining in spinal cord tissue sections of the two groups to assess the differentiation of cBMMSC to neuron-like cells in the nerve conduits after transplantation; the number of BrdU-positive cells was detected to assess the neuronal regeneration of the localized spinal cord injury of the two groups; and the length of axons was observed with laser Confocal photography was used to observe the length of axons; HE staining was used to observe the scarring and cavities in the spinal cord sections of the two groups; immunofluorescence was used to detect neuron-like markers (Nestin, NSE, NF200, GFAP) in the two groups, and the OD values were determined by the Image Processing and Analysis System (IPAAS); and Western blot was used to detect the neurotransmitters of motor fibres, acetylcholinesterase (ChAT), sensory fibres, and sensory fibres, as well as the neurotransmission of motor fibres, acetylcholine production-limiting enzyme (ChAT) and sensory fibre neurotransmitter glutamate synthase (GOGAT); motor function was assessed by BBB score; somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) were detected by body surface electrode assay in the two groups, and the neurophysiological recovery effect was evaluated. Four weeks after transplantation, the NSE content of MAB1281-positive cells in the experimental group was significantly higher than that of the control group; the number of BrdU-positive cells and axon length were significantly greater than that of the control group (p < 0.05); the scarring and cavitation of spinal cord slices were significantly lighter than that of the control group; the expression levels of Nestin, NSE, NF200, GFAP, ChAT, GOGAT, and BBB scores were significantly higher than that of the control group (p < 0.05); SEP and MEP latency time were significantly shorter than that of the control group (p < 0.05), and wave amplitude was significantly greater than that of the control group (p < 0.05). The cBMMSC transplantation based on nanosilver hydrogel nerve conduit was effective in repairing spinal cord injury, promoting neuronal and axonal regeneration, and restoring neuromotor and electrophysiological functions., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Abstract: Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated., (Copyright © 2024 International Association for the Study of Pain.)

Spinal cord injury (SCI) is damage to the spinal cord that permanently or temporarily disrupts its function, causing considerable autonomic, sensory, and motor disorders, and involves between 10 and 83 cases per million yearly. Traumatic SCI happens following primary acute mechanical damage, leading to injury to the spinal cord tissue and worsening clinical outcomes. The present therapeutic strategies for this complex disease fundamentally rely on surgical approaches and conservative remedies. However, these modalities are not effective enough for neurological recovery. Therefore, it is necessary to discover more efficient methods to treat patients with SCI. Today, considerable attention has been drawn to bioactive compounds-based remedies and stem cell therapy for curing various ailments and disorders, such as neurological diseases. Some researchers have recommended that harnessing curcumin, a polyphenol obtained from turmeric, in combination with stem cells, like mesenchymal stem cells, neural stem cells, and ependymal stem cells, can remarkably improve neurological recovery-related parameters more effective than the treatment with these two methods separately in experimental models. Hereby, this literature review delves into the functionality of curcumin combined with stem cells in treating SCI with a focus on cellular and molecular mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Central cord syndrome (CCS) is the most common form of incomplete spinal cord injury, with an increasing incidence with the aging population. This is a clinical diagnosis defined by weakness greater in the upper than lower extremities and often prominent sensory complaints in the hands. CCS is typically seen in individuals with underlying cervical canal stenosis from spondylosis who experience sudden forceful movement of the neck, especially hyperextension, resulting in contusion of the spinal cord. The prognosis in CCS is relatively favorable with improvement in neurological deficits, except for fine motor control of the hands. Neuropathic pain may persist even in those with excellent motor recovery. Nonoperative management may be appropriate in selected patients, but surgery is usually necessary in those with poor neurological recovery or further deterioration. The optimal timing of surgical intervention has not been defined, but recent evidence suggests that early surgery (≤24 h) may lead to greater neurological recovery, shorter hospital stay, and fewer inpatient complications. Management in any given patient must be considered in the context of the anatomy and location of spinal cord compression, the presence of fractures or ligamentous instability, the temporal course of signs and symptoms, as well as the patient's overall health., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Study Design: A narrative review., Objective: To summarize relevant data from representative studies investigating upper limb restorative therapies for cervical spinal cord injury., Summary of Background Data: Cervical spinal cord injury (SCI) is a debilitating condition resulting in tetraplegia, lifelong disability, and reduced quality of life. Given the dependence of all activities on hand function, patients with tetraplegia rank regaining hand function as one of their highest priorities. Recovery from cervical SCI is heterogeneous and often incomplete; currently, various novel therapies are under investigation to improve neurological function and eventually better quality of life in patients with tetraplegia., Methods: In this article, a narrative literature review was performed to identify treatment options targeting the restoration of function in patients with cervical SCI. Studies were included from available literature based on the availability of clinical data and whether they are applicable to restoration of arm and hand function in patients with cervical SCI., Results: We describe relevant studies including indications and outcomes with a focus on arm and hand function. Different treatment modalities described include nerve transfers, tendon transfers, spinal cord stimulation, functional electrical stimulation, non-invasive brain stimulation, brain-machine interfaces and neuroprosthetics, stem cell therapy, and immunotherapy. As the authors' institution leads one of the largest clinical trials on nerve transfers for cervical SCI, we also describe how patients undergoing nerve transfers are managed and followed at our center., Conclusions: While complete recovery from cervical spinal cord injury may not be possible, novel therapies aimed at the restoration of upper limb motor function have made significant progress toward the realization of complete recovery., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Spinal cord injury (SCI) is a profound medical condition that significantly hampers motor function, imposing substantial limitations on daily activities and exerting a considerable financial burden on patients and their families. The constrained regenerative capacity of endogenous spinal cord tissue, exacerbated by the inflammatory response following the initial trauma, poses a formidable obstacle to effective therapy. Recent advancements in the field, stem cells, biomaterials, and molecular therapy, show promising outcomes. This review provides a comprehensive analysis of tissue engineering and regenerative medicine approaches for SCI treatment, including cell transplantation, tissue-engineered construct implantation, and other potential therapeutic strategies. Additionally, it sheds light on preclinical animal studies and recent clinical trials incorporating these modalities, providing a glimpse into the evolving landscape of SCI management. STATEMENT OF SIGNIFICANCE: The investigation into spinal cord injury (SCI) treatments focuses on reducing long-term impacts by targeting scar inhibition and enhancing regeneration through stem cells, with or without growth factors. Induced pluripotent stem cells (iPSCs) show promise for autologous use, with clinical trials confirming their safety. Challenges include low cell viability and difficulty in targeted differentiation. Biomaterial scaffolds hold potential for improving cell viability and integration, and extracellular vesicles (EVs) are emerging as a novel therapy. While EV research is in its early stages, stem cell trials demonstrate safety and potential recovery. Advancing tissue engineering approaches with biomaterial scaffolds is crucial for human trials., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Gao, Kim, and colleagues recently reported that clonal populations of CD4 + T cells could be detected in mice that underwent spinal cord injury (SCI). A subset of clones mediated enhanced motor recovery and suppressed inflammation. Further studies may point towards novel cell therapies for SCI, for which care is presently supportive only., Competing Interests: Declaration of interests R.M.R. is a venture partner at Third Rock Ventures. He is co-founder and clinical advisor with equity in Abata Therapeutics, a company producing regulatory T cell therapies for autoimmune conditions., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite promising basic science discoveries and a surge in clinical trials, the quest for effective treatments that restore neurological function after spinal cord injury lags on. While "failed" in a conventional sense, emerging solutions to longstanding challenges represent promising steps towards a future with effective interventions. In this personal view, we highlight clinical trials implementing new solutions and their impact on the field. Our perspective is that, ultimately, the integration of shared knowledge, adaptive designs, and a deeper understanding of the intricacies of spinal cord injury holds promise of unlocking of major breakthroughs, leading to improved outcomes for people with spinal cord injury., Competing Interests: Declaration of interests P.S.S. is a member of SCITrialsFinder curation group with no financial conflict of interest to declare. J.L.K.K. previously consulted for Axonis. The authors have no other conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Bioengineered nerve conduits have shown great promise for spinal cord injury (SCI) repair, while their practical values are limited by poor regenerative efficacy and lack of multi-level structural design. Here, inspired by the ingenious anatomy of natural spinal cords, a biomimetic multichannel silk nerve conduit (namely BNC@MSCs/SCs) with multicellular spatiotemporal distributions for effective SCI repair is presented. The biomimetic silk nerve conduit (BNC) with hierarchical channels and aligned pore structures is prepared via a modified directional freeze-casting strategy. Such hierarchical structures provide appropriate space for the mesenchymal stem cells (MSCs) and Schwann cells (SCs) settled in specific channels, which contributes to the generation of BNC@MSCs/SCs resembling the cellular spatiotemporal distributions of natural spinal cords. The in vitro results reveal the facilitated SC migration and MSC differentiation in such BNC@MSCs/SCs multicellular system, which further promotes the tube formation and cell migration of endothelial cells as well as M2 polarization of macrophages. Moreover, BNC@MSCs/SCs can effectively promote the tissue repair and function recovery in SCI rats by attenuating glial scar formation while promoting neuron regeneration and myelin sheath reconstruction. Thus, it is believed that the biomimetic multichannel silk nerve conduits with multicellular spatiotemporal distributions are valuable for SCI repair and other neural tissue regeneration., (© 2024 Wiley‐VCH GmbH.)

Study Design: Qualitative studies., Objectives: Spinal cord injury (SCI) is one of the most devastating injuries to the central nervous system that places a major burden on society. Neuromodulation technology involving spinal cord stimulation (SCS) and sacral nerve modulation (SNM) is a promising technique for patients with SCI. However, there has been no bibliometric analysis of research in this field to date., Setting: Not applicable., Methods: Systematic analyses of countries, institutions, authors, journals, co-cited documents, keywords, genes and diseases were performed. Related gene and disease data from the citexs platform were also reviewed. A total of 7437 articles on SCS and SNM in SCI were retrieved from the Web of Science database. The search time was limited to 1985-01-01 to 2022-12-31., Results: We identified a significant increase in research output on SCS and SNM in SCI in recent years, with a concentrated period of high publication activity. Multiple publications were identified on neuropathic pain, electronic stimulation, TNF, BDNF and STAT3 gene expression, indicating that complications and potential therapeutic strategies for SCI are a key focus in the field., Conclusion: Our study provides insights that may help to advance scientific research and potentially improve outcomes in patients with SCI., (© 2024. The Author(s), under exclusive licence to International Spinal Cord Society.)

Spinal cord injury (SCI) is incurable and raises growing concerns. The main barrier to nerve repair is the complicated inhibitory microenvironment, where single-targeted strategies are largely frustrated. Despite the progress in combinatory therapeutic systems, the development and translation of effective therapies remain a challenge with extremely limited clinical materials. In this study, mesenchymal stem cells are transplanted in combination with sustained release of methylprednisolone through delivery in one composite matrix of a microsphere-enveloped adhesive hydrogel. All the materials used, including the stem cells, drug, and the matrix polymers gelatin and hyaluronan, are clinically approved. The therapeutic effects and safety issues are evaluated on rat and canine SCI models. The implantation significantly promotes functional restoration and nerve repair in a severe long-span rat spinal cord transection model. Distant spinal cord segments and the urinary system are effectively protected against pathologic damage. Moreover, the local sustained drug delivery mitigates the inflammatory microenvironment when overcoming the clinical issue of systemic side effects. The study presents an innovative strategy to achieve safe and efficient combinatory treatment of SCI., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Scaffolds have garnered considerable attention for enhancing neural repairment for spinal cord injury (SCI) treatment. Both microstructural features and biochemical modifications play pivotal roles in influencing the interaction of cells with the scaffold, thereby affecting tissue regeneration. Here, a scaffold is designed with spiral structure and gradient peptide modification (GS) specifically for SCI treatment. The spiral structure provides crucial support and space, while the gradient peptide isoleucine-lysine-valine-alanine-valine (IKVAV) modification imparts directional guidance for neuronal and axonal extension. GS scaffold shows a significant nerve extension induction effect through its interlayer gap and gradient peptide density to dorsal root ganglia in vitro, while in vivo studies reveal its substantial promotion for functional recovery and neural repair. Additionally, the GS scaffold displays impressive drug-loading capacity, mesenchymal stem cell-derived exosomes can be efficiently loaded into the GS scaffold and delivered to the injury site, thereby synergistically promoting SCI repair. Overall, the GS scaffold can serve as a versatile platform and present a promising multifunctional approach for SCI treatment., (© 2024 Wiley‐VCH GmbH.)

Background: This study investigates the potential of transcranial magnetic stimulation (TMS) to enhance spinal cord axon regeneration by modulating corticospinal pathways and improving motor nerve function recovery in rats with spinal cord injury (SCI)., New Method: TMS is a non-invasive neuromodulation technique that generates a magnetic field to activate neurons in the brain, leading to depolarization and modulation of cortical activity. Initially utilized for brain physiology research, TMS has evolved into a diagnostic and prognostic tool in clinical settings, with increasing interest in its therapeutic applications. However, its potential for treating motor dysfunction in SCI has been underexplored., Results: The TMS intervention group exhibited significant improvements compared to the control group across behavioral assessments, neurophysiological measurements, pathological analysis, and immunological markers., Comparison With Existing Methods: Unlike most studies that focus on localized spinal cord injury or muscle treatments, this study leverages the non-invasive, painless, and highly penetrating nature of TMS to focus on the corticospinal tracts, exploring its therapeutic potential for SCI., Conclusions: TMS enhances motor function recovery in rats with SCI by restoring corticospinal pathway integrity and promoting axonal regeneration. These findings highlight TMS as a promising therapeutic option for SCI patients with currently limited treatment alternatives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)