Treatment Of Spinal Cord Injury Research Articles

A Functionalized Scaffold Facilitates Neurites Extension for Spinal Cord Injury Therapy.

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.

Advances and Challenges in Spinal Cord Injury Treatments

Spinal cord injury (SCI) is a debilitating condition that is associated with long-term physical and functional disability. Our understanding of the pathogenesis of SCI has evolved significantly over the past three decades. In parallel, significant advances have been made in optimizing the management of patients with SCI. Early surgical decompression, adequate bony decompression and expansile duraplasty are surgical strategies that may improve neurological and functional outcomes in patients with SCI. Furthermore, advances in the non-surgical management of SCI have been made, including optimization of hemodynamic management in the critical care setting. Several promising therapies have also been investigated in pre-clinical studies, with some being translated into clinical trials. Given the recent interest in advancing precision medicine, several investigations have been performed to delineate the role of imaging, cerebral spinal fluid (CSF) and serum biomarkers in predicting outcomes and curating individualized treatment plans for SCI patients. Finally, technological advancements in biomechanics and bioengineering have also found a role in SCI management in the form of neuromodulation and brain–computer interfaces.

The therapeutic potential of fibroblast growth factors in spinal cord injury: Roles and applications for neuroprotection

Spinal cord injury (SCI) is a severe and debilitating condition that often leads to significant and permanent neurological deficits, affecting motor, sensory, and autonomic functions. The high prevalence of SCI and the lack of effective treatments make it a critical area of medical research. Recent studies have shown promising prospects for fibroblast growth factors (FGF) in the treatment of SCI. FGF, particularly FGF-1 and FGF-2, are known to promote cell growth, differentiation, and survival, and have been demonstrated to enhance axonal regeneration and functional recovery in SCI models. This review highlights the roles of various FGF in neuroprotection, axonal regeneration, and remyelination. It also discusses the potential therapeutic applications of FGF in SCI treatment, emphasizing their ability to reduce neuroinflammation, oxidative stress, and promote motor function recovery. The comprehensive overview of existing research underscores the importance of FGF in SCI repair and suggests further exploration into their therapeutic potential.

Stem Cell Therapies for Spinal Cord Injury - A Review

The escalating incidence of Spinal Cord Injury (SCI), with approximately 0.9 million cases globally, underscores its growing public health concern. Traumatic SCI, often prevalent in developing nations due to factors like motor vehicle accidents and falls, leads to secondary damage involving inflammation, neuronal death, and ionic dysregulation. Despite the absence of an effective treatment for SCI, Stem Cell Therapy (SCT) emerges as a promising avenue, harnessing stem cells' unique capabilities for regeneration and replacement. The review explores various stem cell types, such as Neural Stem/Progenitor Cells (NS/PCs), Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), and Mesenchymal Stem Cells (MSCs), detailing their potential in preclinical and clinical contexts. Specifically, NSCs exhibit therapeutic promise by modulating astrocyte contribution, enhancing differentiation, and promoting growth factors. ESCs, despite their pluripotency, face ethical concerns and potential teratocarcinoma formation. IPSCs, reprogrammed from somatic cells, showcase potential in treating SCI without ethical issues. MSCs, with diverse sources like bone marrow, umbilical cord, and adipose tissue, offer versatility in differentiation and therapeutic benefits. Clinical trials with MSCs, especially BM-MSCs, UC-MSCs, and AD-MSCs, demonstrate improvements in motor and sensory functions, highlighting their regenerative potential. Despite promising results, challenges such as potential tumorigenesis and high costs persist, warranting further exploration and clinical translation of these stem cell therapies for SCI.

Stem Cell Therapies for Spinal Cord Injury - A Review

The escalating incidence of Spinal Cord Injury (SCI), with approximately 0.9 million cases globally, underscores its growing public health concern. Traumatic SCI, often prevalent in developing nations due to factors like motor vehicle accidents and falls, leads to secondary damage involving inflammation, neuronal death, and ionic dysregulation. Despite the absence of an effective treatment for SCI, Stem Cell Therapy (SCT) emerges as a promising avenue, harnessing stem cells' unique capabilities for regeneration and replacement. The review explores various stem cell types, such as Neural Stem/Progenitor Cells (NS/PCs), Embryonic Stem Cells (ESCs), Induced Pluripotent Stem Cells (iPSCs), and Mesenchymal Stem Cells (MSCs), detailing their potential in preclinical and clinical contexts. Specifically, NSCs exhibit therapeutic promise by modulating astrocyte contribution, enhancing differentiation, and promoting growth factors. ESCs, despite their pluripotency, face ethical concerns and potential teratocarcinoma formation. IPSCs, reprogrammed from somatic cells, showcase potential in treating SCI without ethical issues. MSCs, with diverse sources like bone marrow, umbilical cord, and adipose tissue, offer versatility in differentiation and therapeutic benefits. Clinical trials with MSCs, especially BM-MSCs, UC-MSCs, and AD-MSCs, demonstrate improvements in motor and sensory functions, highlighting their regenerative potential. Despite promising results, challenges such as potential tumorigenesis and high costs persist, warranting further exploration and clinical translation of these stem cell therapies for SCI.

Mechanism Analysis of Selenium-Containing Compounds in Alleviating Spinal Cord Injury Based on Network Pharmacology and Molecular Docking Technology.

Spinal cord injury (SCI) is a severe traumatic condition in spinal surgery characterized by nerve damage in and below the injured area. Despite advancements in understanding the pathophysiology of SCI, effective clinical treatments remain elusive. Selenium compounds have become a research hotspot due to their diverse medicinal activities. Previously, our group synthesized a selenium-containing Compound 34# with significant anti-inflammatory activity. This study aimed to explore the anti-SCI effects of selenium-containing compounds using network pharmacology, molecular docking (MD), and ADMET methods. To identify SCI-related targets and those associated with 34#, GeneCards, NCBI, and SEA databases were employed. Eight overlapping targets were considered candidate targets, and molecular docking was performed using the PDB database and AutoDock software. The STRING database was used to obtain protein-protein interactions (PPI). Molecular dynamics simulation, MM/GBSA binding free energy score, and ADMET prediction were used to evaluate the potential targets and drug properties of 34#. Finally, experiments on NSC34 cells and mice were to verify the effects of 34# on SCI. Our results revealed eight candidate targets for 34# in the treatment of SCI. PPI and MD identified ADRB2 and HTR1F as the highest connectivity with 34#. ADMET analysis confirmed the low toxicity and safety of 34#. In vitro and in vivo models validated the anti-SCI effects. Our study elucidated candidate targets for alleviating SCI with 34#, explored PPI and target-related signaling pathways, and validated its anti-SCI effects. These findings enhance our understanding of 34#'s mechanism in treating SCI, positioning it as a potential candidate for SCI prevention.

Low frequency of repetitive trans-spinal magnetic stimulation promotes functional recovery after spinal cord injury in mice through inhibiting TGF-β1/Smad2/3 signaling pathway

Spinal cord injury (SCI) remains a worldwide challenge due to limited treatment strategies. Repetitive trans-spinal magnetic stimulation (rTSMS) is among the most cutting-edge treatments for SCI. However, the mechanism underlying rTSMS on functional recovery is still unclear. In this study, 8-week-old C57BL/6J female mice were used to design SCI models followed by treatment with monotherapy (1 Hz rTSMS or LY364947) or combination therapy (rTSMS + LY364947). Our results showed obvious functional recovery after monotherapies compared to untreated mice. Immunofluorescence results demonstrated that rTSMS and LY364947 modulate the lesion scar by decreasing fibrosis and GFAP and possess the effect on neural protection. In addition, rTSMS suppressed inflammation and the activation of TGFβ1/Smad2/3 signaling pathway, as evidenced by markedly reduced TGF-βRⅠ, Smad2/3, and p-Smad2/3 compared with untreated mice. Overall, it was confirmed that 1 Hz rTSMS promotes SCI recovery by suppressing the TGFβ1/Smad2/3 signaling, revealing a novel pathological mechanism of 1 Hz rTSMS intervention, and may provide potential targets for clinical treatment.

Decellularized porcine peripheral nerve based injectable hydrogels as a Schwann cell carrier for injured spinal cord regeneration

Objective. To develop a clinically relevant injectable hydrogel derived from decellularized porcine peripheral nerves and with mechanical properties comparable to native central nervous system (CNS) tissue to be used as a delivery vehicle for Schwann cell transplantation to treat spinal cord injury (SCI). Approach. Porcine peripheral nerves (sciatic and peroneal) were decellularized by chemical decellularization using a sodium deoxycholate and DNase (SDD) method previously developed by our group. The decellularized nerves were delipidated using dichloromethane and ethanol solvent and then digested using pepsin enzyme to form injectable hydrogel formulations. Genipin was used as a crosslinker to enhance mechanical properties. The injectability, mechanical properties, and gelation kinetics of the hydrogels were further analyzed using rheology. Schwann cells encapsulated within the injectable hydrogel formulations were passed through a 25-gauge needle and cell viability was assessed using live/dead staining. The ability of the hydrogel to maintain Schwann cell viability against an inflammatory milieu was assessed in vitro using inflamed astrocytes co-cultured with Schwann cells. Main results. The SDD method effectively removes cells and retains extracellular matrix in decellularized tissues. Using rheological studies, we found that delipidation of decellularized porcine peripheral nerves using dichloromethane and ethanol solvent improves gelation kinetics and mechanical strength of hydrogels. The delipidated and decellularized hydrogels crosslinked using genipin mimicked the mechanical strength of CNS tissue. The hydrogels were found to have shear thinning properties desirable for injectable formulations and they also maintained higher Schwann cell viability during injection compared to saline controls. Using in vitro co-culture experiments, we found that the genipin-crosslinked hydrogels also protected Schwann cells from astrocyte-mediated inflammation. Significance. Injectable hydrogels developed using delipidated and decellularized porcine peripheral nerves are a potential clinically relevant solution to deliver Schwann cells, and possibly other therapeutic cells, at the SCI site by maintaining higher cellular viability and increasing therapeutic efficacy for SCI treatment.

Therapeutic effect and mechanism of piracetam for the treatment of spinal cord injury in rats through MAPK pathway

To explore mechanism of piracetam for the treatment of spinal cord injury in rats through mitogen-activated protein kinase (MAPK) pathway. Fifty-four healthy 6-week-old SD female rats with body weight of 80 to 100 g were divided into sham operation group, spinal cord injury group and piracetam group by random number table method, with 18 rats in each group. Spinal cord injury model was established in spinal cord injury group and piracetam group using percussion apparatus, while sham operation group did not damage spinal cord. Piracetam group was injected with piracetam injection through tail vein according to 5 ml·kg-1 standard, once a day for 3 days;the other two groups were injected with normal saline at the same dose, the same frequency and the same duration. The rats were sacrificed at 1, 3, and 7 days after surgery, and changes of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was observed and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect spinal cord inflammatory factors, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (interleukin-1β), necrosis factor-α (IL-1β) and tumor necrosis factor-α (TNF-α);HE staining was used to observe morphological changes of rats with spinal cord injury, and immunohistochemistry was used to observe expression level of aquaporin 4 (AQP4). The activation of MAPK signaling pathway in spinal cord of rats after spinal cord injury was observed by western blotting (WB). BBB scores of sham operation group on 1, 3 and 7 day were 21 points. In spinal cord injury group, the scores were (1±1), (4±1) and (7±2);piracetam group was (1±1), (5±1), (9±2), respectively;the difference between spinal cord injury group and sham operation group was statistically significant (P<0.05). HE staining showed that no abnormality was found in sham operation group. In spinal cord injury group, bleeding and degeneration of spinal cord tissue appeared at 1 day after operation; flaky necrotic areas were appeared in spinal cord at 3 days after surgery, and spinal cord tissue began to slowly repair at 7 days after surgery. In piracetam group, the bleeding area was less than that of spinal cord injury group at 1 day after surgery;at 3 days after operation, the necrotic area was reduced and the range of nuclear disappearance was reduced; and the spinal cord began to recover slowly at 7 days after surgery. AQP4 staining of spinal cord of rats in sham operation group was weak at 1, 3 and 7 days after modeling, AQP4 staining was deepened and area increased in spinal cord injury group, AQP4 staining of piracetam group was lighter than that of spinal cord injury group, and the positive cells were slightly increased and the staining was slightly darker than that of sham operation group. At 1, 3 and 7 days, the level of IL-6, IL-10, IL-1β and TNF-α in spinal cord injury group were higher than those in sham operation group and piracetam group(P<0.05). Compared with spinal cord injury group, the area of spinal cord bleeding and necrosis were decreased by HE staining in piracetam group, and AQP4 staining was decreased by immunohistochemistry. WB results showed that P-ERK, P-JNK and P-P38 levels in spinal cord injury group at 3 days were higher than those in sham operation group and piracetam group(P<0.05). Piracetam not only showed significant effect in promoting motor function recovery after spinal cord injury, but also showed positive therapeutic potential in reducing lesion area, regulating AQP4 expression to reduce edema, and reducing inflammatory response by regulating MAPK signaling pathway.

Time from injury to acute surgery for patients with traumatic cervical spinal cord injury in South-East Norway.

The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were ≥65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day.

Identification of coagulation diagnostic biomarkers related to the severity of spinal cord injury

BackgroundBlood always shows coagulation changes after spinal cord injury (SCI), and identifying these blood changes may be helpful for diagnosis and treatment of SCI. Nevertheless, studies to date on blood coagulation changes after SCI in humans are not comprehensive. Therefore, this study aims to identify blood coagulation diagnostic biomarkers and immune changes related to SCI and its severity levels. MethodsHuman blood sequencing datasets were obtained from public databases. Differentially expressed coagulation-related genes were analyzed (DECRGs). Enrichment analysis and assessment of immune changes were conducted. Weighted gene co-expression network analysis, least absolute shrinkage and selection operator logistic regression were used to identify biomarkers. Validation for these biomarkers was performed. The correlation between biomarkers and immune cells was evaluated. Transcription factors, miRNA, lncRNA, and drugs that can regulate biomarkers were analyzed. ResultsDECRGs associated with SCI and its different grades were identified, showing enrichment in altered coagulation and immune-related signaling pathways. ADAM9, CD55, and STAT4 were identified as coagulation diagnostic biomarkers for SCI. IRF4 and PABPC4 were identified as coagulation diagnostic biomarkers for American Spinal Injury Association Impairment Scale (AIS) A grade of SCI. GP9 was designated as a diagnostic biomarker for AIS D grade of SCI. Immune changes in blood of SCI and its different grades were observed. Correlation between diagnostic biomarkers and immune cells were identified. Transcription factors, miRNA, lncRNA, and drugs that can regulate diagnostic biomarker expression were discovered. ConclusionTherefore, detecting the expression of these putative diagnostic biomarkers and related immune changes may be helpful for predicting the severity of SCI. Uncovering potential regulatory mechanisms for biomarkers may be beneficial for further research.

MiR-540-3p partially recovers the locomotor function of spinal cord injury mice by targeting SIX4/Yap1 and inactivation of astrocytes

ABSTRACT Background Spinal cord injury (SCI) lacks therapeutic reagents. miRNAs are responsible for mesenchymal stem cells (MSCs) therapy in spinal cord injury. Purpose To discover the underlying therapeutic miRNA target and its mechanism for the treatment of SCI. Method Two RNA sequence datasets were retrieved from the GEO Datasets database which was accessed on 30 December 2023. The targets of the top 2 ranked miRNAs (miR-540-3p and miR-433-5p) were analyzed using online databases (miRDB, miRMap, TargetScan and STRING database) and both miRNAs were screened by cell counting kit-8 (CCK-8) assay. Then, transfection and local injection of miR-540-3p were performed to examine the capacity of secretion of astrocytes and the locomotor function of SCI mice. Results The significantly high levels of miR-540-3p/433-5p were revealed. Transfection of miR-540-3p conferred inactivation of reactive astrocytes and weakened the capacity of secreting inflammatory cytokines of astrocytes. miR-433-5p was proven to not impact the proliferation of astrocytes. Co-culture of culture supernate from astrocytes transfected with miR-540-3p and neurons demonstrated the significantly preserved neurite length and decreased apoptotic level of neurons. Meanwhile, sine oculis homeobox (SIX4)/Yap1, as the target of miR-540-3p, is critical for abrogating inflammatory damage of neurons in vivo and in vitro, decreasing glial scar, and recovering locomotor function of spinal cord injury mice. Furthermore, SCI mice receiving a local injection of miR-540-3p showed smaller and lighter bladder volume and higher limb strength, but the period from urinary retention to autonomous urination of SCI mice showed no significance. Conclusions Conclusively, miR-540 discovered from hypoxia-treated exosomes suppresses the inflammatory cytokines secreted by reactive astrocytes, partially preserves the neuronal function of spinal cord injury mice, through the SIX4/Yap1 signalling pathway.

Microglia-mediated pericytes migration and fibroblast transition via S1P/S1P3/YAP signaling pathway after spinal cord injury

Platelet-derived growth factor receptor β positive (PDGFRβ+) pericytes detach from the microvascular wall and migrate into the injury center following spinal cord injury (SCI), which has been widely regarded as the main source of fibrotic scar, but the mechanism of migration and fibroblast transition remains elusive. Here we show the associated spatiotemporal distribution between microglia and pericytes at three and seven days post-injury (dpi). The increased expression of Sphingosine kinase-1 (SPHK1) in microglia significantly raised the concentration of Sphingosine-1-phosphate (S1P) in the spinal cord, which promotes migration and fibroblast transition of pericyte. In vitro experiments, we found the elevated Sphingosine 1-phosphate receptor 3 (S1P3), the S1P/S1PR3 axis inhibited the phosphorylation of YAP and promoted its nuclear translocation, which contributed to the formation of alpha-smooth muscle actin (α-SMA) and collagen type I (COL1) protein, This process can be blocked by an S1P3 specific inhibitor TY52156 in vitro. The S1P/S1P3/YAP pathway might be a potential target for treatment in SCI.

Can a complete excision of the injured site of the spinal cord lead to positive results?

Until now, there are no successful ways to restore the damaged spinal cord and its functions in severe spinal cord injury such as spinal cord contusion, rupture or intersection. This is largely due to the lack of treatment methods aimed at the chain of pathogenetic processes occurring in the nervous tissue after injury. The topic of restoration of spinal cord functions is taboo, often undesirable for discussion, and is influenced by clinical stereotypes. The article proposes to consider the method of treatment of spinal cord injury, using modern data, taking into account emerging pathophysiological processes at the site of injury and beyond. The use of new data and achievements of experimental science on severe spinal cord injury can be a serious step towards the development of new methods for the treatment of this pathology.

Optical Devices for the Diagnosis and Management of Spinal Cord Injuries: A Review.

Throughout the central nervous system, the spinal cord plays a very important role, namely, transmitting sensory and motor information inwardly so that it can be processed by the brain. There are many different ways this structure can be damaged, such as through traumatic injury or surgery, such as scoliosis correction, for instance. Consequently, damage may be caused to the nervous system as a result of this. There is no doubt that optical devices such as microscopes and cameras can have a significant impact on research, diagnosis, and treatment planning for patients with spinal cord injuries (SCIs). Additionally, these technologies contribute a great deal to our understanding of these injuries, and they are also essential in enhancing the quality of life of individuals with spinal cord injuries. Through increasingly powerful, accurate, and minimally invasive technologies that have been developed over the last decade or so, several new optical devices have been introduced that are capable of improving the accuracy of SCI diagnosis and treatment and promoting a better quality of life after surgery. We aim in this paper to present a timely overview of the various research fields that have been conducted on optical devices that can be used to diagnose spinal cord injuries as well as to manage the associated health complications that affected individuals may experience.

Safety and Efficacy of Bone Marrow and Adipose Tissue Mesenchymal Stem Cells in the Treatment of Spinal Cord Injury: A Preliminary Study

Safety and Efficacy of Bone Marrow and Adipose Tissue Mesenchymal Stem Cells in the Treatment of Spinal Cord Injury: A Preliminary Study

Advances of the MAPK pathway in the treatment of spinal cord injury.

Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen-activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post-SCI. Modulating this pathway post-injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.

Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1

Spinal cord injury (SCI) is a serious trauma of the central nervous system. The clearance of myelin debris is a critical step in the functional recovery following spinal cord injury (SCI). Recent studies have begun to reveal critical roles for professional phagocytes in the central nervous system, microglia, and their receptors in the control of myelin debris in neurodegenerative disease. Repeated trans-spinal magnetic stimulation (rTSMS) has been demonstrated as a noninvasive SCI treatment that enhances tissue repair and functional recovery. In this study, we investigated the role and molecular mechanism of rTSMS on microglial phagocytosis of myelin debris in a rat SCI model. In our studies, we found that rTSMS significantly promoted the motor function recovery of SCI rats associated with the inhibition the neuroinflammation and glia scar formation. Immunofluorescence results further showed that the rTSMS promotes the clearance of myelin debris by microglia in vivo and in vitro. Additionally, receptor-associated protein (RAP), a Low-density lipoprotein receptor-related protein-1 (LRP-1) inhibitor, could cancel the accelerated microglial phagocytosis of myelin debris after rTSMS in vitro experiments. Simultaneously, Elisa's results and western blotting respectively showed that rTSMS significantly decreased the levels of soluble LRP-1(sLRP-1) and the LRP-1 splicing enzyme of ADAM17. In conclusion, rTSMS could promote the clearance of myelin debris by microglia through LRP-1 to improve the functional recovery of SCI rats.

Schwann Cell-Derived Exosomes Induced Axon Growth after Spinal Cord Injury by Decreasing PTP-σ Activation on CSPGs via the Rho/ROCK Pathway.

Spinal cord injury (SCI) is a severe neurological condition that involves a lengthy pathological process. This process leads to the upregulation of chondroitin sulfate proteoglycans (CSPGs) by reactive glia, which impedes repair and regeneration in the spinal cord. The role of the CSPG-specific receptor protein tyrosine phosphatase-sigma (PTP-σ) in post-SCI remains largely unexplored. Exosomes have great potential in the diagnosis, prognosis, and treatment of SCI due to their ability to easily cross the blood‒brain barrier. Schwann cell-derived exosomes (SCDEs) promote functional recovery in mice post-SCI by decreasing CSPG deposition. However, the mechanism by which SCDEs decrease CSPGs after SCI remains unknown. Herein, we observed elevated levels of PTP-σ and increased CSPG deposition during glial scar formation after SCI in vivo. After SCDEs were injected into SCI mice, CSPG deposition decreased in scar tissue at the injury site, the expression of PTP-σ increased during axonal growth around the injury site, and motor function subsequently recovered. Additionally, we demonstrated that the use of both Rho/ROCK inhibitors and SCDEs inhibited the reparative effects of SCDEs on scar tissue after SCI. In conclusion, our study revealed that treatment with SCDEs targeting the Rho/ROCK signaling pathway reduced PTP-σ activation in the CSPG post-SCI, which inhibited scar tissue formation.

The Syvn1 inhibits neuronal cell ferroptosis by activating Stat3/Gpx4 axis in rat with spinal cord injury.

Spinal cord injury (SCI) leads to secondary neuronal death, which severely impedes recovery of motor function. Therefore, prevention of neuronal cell death after SCI is an important strategy. Ferroptosis, a new form of cell death discovered in recent years, has been shown to be involved in the regulation of SCI. However, the role and potential mechanisms of ferroptosis in secondary SCI are not fully understood. In this study, we report that the E3 ubiquitin ligase Syvn1 suppresses ferroptosis and promotes functional recovery from SCI in vitro and in vivo. Mechanistically, screened with bioinformatics, immunoprecipitation, and mass spectrometry, we identified Stat3, a transcription factor that induces the expression of the ferroptosis inhibitor Gpx4, as a substrate of Syvn1. Furthermore, we identified neurons as the primary cellular source of Syvn1 signalling. Moreover, we determined the binding domains of Syvn1 and Stat3 in HEK 293 T cells using full-length proteins and a series of truncated Flag-tagged and Myc-tagged fragments. Furthermore, we created the cell and animal models with silencing or overexpression of Syvn1 and Stat3 and found that Syvn1 inhibits neuronal ferroptosis by stabilizing Stat3, which subsequently activates the ferroptosis regulator Gpx4 in SCI. In summary, the Syvn1-mediated Stat3/Gpx4 signalling axis attenuates neuronal ferroptosis, reduces neuronal death, and promotes SCI repair. Therefore, our findings provide potential new targets and intervention strategies for the treatment of SCI.