Recovery Of Spinal Cord Function Research Articles

Decompression and reconstruction the spinal TB lesion of a single vertebra through thoracoscopy alone or combined with foraminal endoscopy

ObjectiveThis study aimed to compare the clinical efficacy of thoracoscopy combined with transforaminal endoscopy and thoracoscopy alone in the treatment of thoracic tuberculosis.MethodsPatients with thoracic tuberculosis who visited our hospital from February 2018 to October 2022 were retrospectively analyzed. The patients were divided into thoracoscopic combined transforaminal endoscopic surgery group (group A) and thoracoscopic surgery alone group (group B) according to the surgical methods. Surgery-related information, VAS score, ODI score, degree of spinal cord function improvement, fusion time, and progression of kyphotic deformity were compared.ResultsA total of 37 patients were included, 16 in group A and 21 in group B. Postoperative follow-up time was 10–48 months, with an average of 28.62 ± 10.53 months. All patients had significant improvement in chest and back pain and spinal cord function after the operation. There were statistical differences in operation time, intraoperative blood loss, incidence rate of complications, and JOA score at 1 week and 3 months after operation between the two groups (P<0.05). There was no significant difference in VAS, ODI score, kyphotic angle correction, kyphotic correction loss angle, postoperative drainage volume, and fusion time between the two groups (P>0.05). All patients had no recurrence of thoracic tuberculosis during follow-up.ConclusionThoracoscopy combined with transforaminal endoscopy produce equivalent long-term results with shorter operation time, less intraoperative blood loss, less complications and higher surgical safety comparing to thoracoscopy alone. And thoracoscopy combined with transforaminal endoscopy can fully decompress and facilitate the early recovery of spinal cord function.

Comparison of the accuracy and safety of robot-and navigation-assisted screw placement in atlantoaxial dislocation surgery

Objective: To compare the accuracy and safety of robot-assisted and navigation-assisted screw placement in atlantoaxial dislocation surgery. Methods: A retrospective analysis was conducted on the clinical data of 49 patients with atlantoaxial dislocation treated consecutively at the Honghui Hospital of Xi'an Jiaotong University from April 2022 to December 2023. Among them, 27 were male and 22 were female, aged (44.2±11.7) years. Based on the date of surgery, 29 patients (from April 2022 to April 2023) received the S8 navigation-assisted screw placement (navigation group), 20 patients (from May to December 2023) received Mazor robot-assisted screw placement (robot group). The accuracy of screw placement, screw placement time, operation time, intraoperative blood loss, and intraoperative complications were recorded and compared between the two groups. The Japanese Orthopedic Association (JOA) score and visual analog scale (VAS) score of pain were adopted to evaluate the recovery of cervical spinal cord function and cervical and shoulder pain at preoperative period and 3-month follow-up, and the occurrence of complications was observed. Results: A total of 196 screws were inserted in 49 patients. In the navigation-assisted group, a total of 116 screws were inserted with an accuracy rate of 93.1% (108/116); in contrast, in the robot-assisted group, a total of 80 screws were inserted with an accuracy rate of 97.5% (78/80) (P=0.040). The mean screw placement time, operation time, and blood loss in the navigation-assisted group were all significantly lower than those in the robot-assisted group [(37.8±3.4)min vs (48.4±4.6)min, (127.7±15.3)min vs (165.7±12.1)min and (205.8±13.6)ml vs (290.6±11.2) ml, respectively all P<0.01]. One case experienced intraoperative venous plexus injury in the robot-assisted group. Postoperatively, all patients experienced significant relief in neck pain symptoms, and neurological symptoms recovered to varying degrees. The VAS and JOA scores at 3 months post-surgery for both groups showed statistically significant improvements compared to pre-surgery (all P<0.01), but there was no statistically significant difference between the two groups (all P>0.05). Conclusions: Both robot-assisted and navigation-assisted screw placement show high accuracy and safety in atlantoaxial dislocation surgery. Compared to navigation, robot assistance increases the surgical time and blood loss, but significantly improves the accuracy of screw placement.

Case report: a rare case of intradural and pleural wall cystic echinococcosis

BackgroundCystic echinococcosis (CE) is prevalent in livestock farming regions around the world. However, it remains relatively rare compared to other infectious diseases. CE typically affects the liver, lungs, brain, and kidneys. Spinal and pleural wall involvement is exceedingly rare. We report a unique case of intradural and pleural wall CE in a young male, successfully treated with surgery and postoperative medication.Case presentationA 19-year-old Tibetan male from the Qinghai-Tibet Plateau was diagnosed with intradural and pleural wall CE through imaging, serology, and surgical pathology. According to the Dew/Braithwaite & Lees (BL) classification, his condition was an exceptionally rare form of spinal echinococcosis, compounded by an even rarer pleural wall involvement. Prompt surgical intervention and postoperative medication resulted in significant improvement in spinal cord compression symptoms.ConclusionsThis case highlights the diagnostic and therapeutic challenges of rare CE locations. MRI proved superior to CT in diagnosing bony cystic echinococcosis. Early surgical intervention combined with medication facilitates spinal cord function recovery, providing valuable insights for managing similar cases.

A biomimic anti-neuroinflammatory nanoplatform for active neutrophil extracellular traps targeting and spinal cord injury therapy

Traumatic spinal cord injury (SCI) always leads to severe neurological deficits and permanent damage. Neuroinflammation is a vital process of SCI and have become a promising target for SCI treatment. However, the neuroinflammation-targeted therapy would hinder the functional recovery of spinal cord and lead to the treatment failure. Herein, a biomimic anti-neuroinflammatory nanoplatform (DHCNPs) was developed for active neutrophil extracellular traps (NETs) targeting and SCI treatment. The curcumin-loaded liposome with the anti-inflammatory property acted as the core of the DHCNPs. Platelet membrane and neutrophil membrane were fused to form the biomimic hybrid membrane of the DHCNPs for hijacking neutrophils and neutralizing the elevated neutrophil-related proinflammatory cytokines, respectively. DNAse I modification on the hybrid membrane could achieve NETs degradation, blood spinal cord barrier, and neuron repair. Further studies proved that the DHCNPs could reprogram the multifaceted neuroinflammation and reverse the SCI process via nuclear factor kappa-B (NF-κB) pathway. We believe that the current study provides a new perspective for neuroinflammation inhibition and may shed new light on the treatment of SCI.

Design and preparation of hydrogel microspheres for spinal cord injury repair.

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.

Potential Roles of Specific Subclasses of Premotor Interneurons in Spinal Cord Function Recovery after Traumatic Spinal Cord Injury in Adults.

The differential expression of transcription factors during embryonic development has been selected as the main feature to define the specific subclasses of spinal interneurons. However, recent studies based on single-cell RNA sequencing and transcriptomic experiments suggest that this approach might not be appropriate in the adult spinal cord, where interneurons show overlapping expression profiles, especially in the ventral region. This constitutes a major challenge for the identification and direct targeting of specific populations that could be involved in locomotor recovery after a traumatic spinal cord injury in adults. Current experimental therapies, including electrical stimulation, training, pharmacological treatments, or cell implantation, that have resulted in improvements in locomotor behavior rely on the modulation of the activity and connectivity of interneurons located in the surroundings of the lesion core for the formation of detour circuits. However, very few publications clarify the specific identity of these cells. In this work, we review the studies where premotor interneurons were able to create new intraspinal circuits after different kinds of traumatic spinal cord injury, highlighting the difficulties encountered by researchers, to classify these populations.

Succinic acid modified chitosan hydrogel mediates in-situ bioenergetic remodeling of neural cells for neuronal differentiation and spinal cord injury repair

A primary challenge in spinal cord injury repair is the presence of an energy deficit, exacerbated by the injury itself, thereby intensifying the dilemma of insufficient energy. Hence, we posit a hypothesis suggesting that the adoption of a direct energy-supply material strategy has the potential to enhance in situ cellular energy levels, facilitating the acceleration of neuronal differentiation and axonal elongation. We successfully designed a degradable bioenergetic hydrogel by introducing succinic acid (SA), a key intermediate in tricarboxylic acid (TCA) cycle, into chitosan (CS) as an energy-active unit, which was released in a sustained degradation-mediated fashion once implanted. The degraded energy-active units, after being internalized, increased bioenergetic levels via oxidative phosphorylation (OXPHOS) by facilitating TCA flux, thereby contributing to a at least 1.5-fold increase in the expression levels of neuronal differentiation-related markers in vitro, as well as the enhanced spinal cord injury repair and functional recovery in vivo. Further mechanism analysis demonstrated that the upregulation of the bioenergetic basis had the potential to induce neuronal differentiation through the AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) axis. Additionally, the adenosine triphosphate (ATP) itself acted as a signaling molecule via the P2X7 receptor, leading to the upregulation of intracellular calcium ion-MAPK signal cascades, ultimately promoting neuronal differentiation. Overall, these findings have the potential to significantly alter our understanding of cell metabolism and energy homeostasis, transforming them from passive observers to critical factors in guiding nerve regeneration, and may have implications for future design of bioenergetic-active materials.

The Role of Exosomes from Mesenchymal Stem Cells in Spinal Cord Injury: A Systematic Review.

Spinal cord injury (SCI) is a serious nervous system disease that usually leads to the impairment of the motor, sensory, and autonomic nervous functions of the spinal cord, and it places a heavy burden on families and healthcare systems every year. Due to the complex pathophysiological mechanism of SCI and the poor ability of neurons to regenerate, the current treatment scheme has very limited effects on the recovery of spinal cord function. In addition, due to their unique advantages, exosomes can be used as carriers for cargo transport. In recent years, some studies have confirmed that treatment with mesenchymal stem cells (MSCs) can promote the recovery of SCI nerve function. The therapeutic effect of MSCs is mainly related to exosomes secreted by MSCs, and exosomes may have great potential in SCI therapy. In this review, we summarized the repair mechanism of mesenchymal stem cells-derived exosomes (MSCs-Exos) in SCI treatment and discussed the microRNAs related to SCI treatment based on MSCs-Exos and their mechanism of action, which is helpful to further understand the role of exosomes in SCI.

Transplantation of Heat-Shock Preconditioned Neural Stem/Progenitor Cells Combined with RGD-Functionalised Hydrogel Promotes Spinal Cord Functional Recovery in a Rat Hemi-Transection Model.

Neural stem/progenitor cell (NSPC) transplantation in spinal cord injury (SCI) is a potential treatment that supports regeneration by promoting neuroprotection, remyelination, and neurite outgrowth. However, glial scarring hinders neuroregeneration and reduces the efficiency of cell transplantation. The present study aimed to enhance this neuroregeneration by surgically removing the glial scar and transplanting heat-shock (HS) preconditioned NSPCs in combination with Arg-Gly-Asp (RGD)-functionalised hydrogel in a rat spinal cord hemi-transection model. Twelve Sprague-Dawley rats underwent spinal cord hemi-transection and were randomly divided into three treatment groups: hydrogel implantation (control group), NSPC-encapsulated hydrogel implantation, and HS-NSPC-encapsulated hydrogel implantation. HS preconditioning was applied to the NSPCs to reinforce cell retention and an RGD-functionalised hydrogel was used as a biomatrix. In vitro culture showed that preconditioned NSPCs highly differentiated into neurons and oligodendrocytes and exhibited higher proliferation and neurite outgrowth in hydrogels. Rats in the HS-NSPC-encapsulated hydrogel implantation group showed significantly improved functional recovery, neuronal and oligodendrocyte differentiation of transplanted cells, remyelination, and low fibrotic scar formation. The surgical removal of the glial scar in combination with HS-preconditioning and RGD-functionalised hydrogels should be considered as a new paradigm in NSPC transplantation for spinal cord regeneration treatment.

Asiaticoside Attenuates Blood-Spinal Cord Barrier Disruption by Inhibiting Endoplasmic Reticulum Stress in Pericytes After Spinal Cord Injury.

The blood-spinal cord barrier (BSCB) plays a vital role in the recovery of spinal cord function after spinal cord injury (SCI). Pericytes, pluripotent members of the neurovascular unit (NVU), receive signals from neighboring cells and are critical for maintaining CNS function. Therapeutic targets for the BSCB include endothelial cells (ECs) and glial cells, but few drugs target pericytes. This study was designed to explore whether asiaticoside has a positively effect on pericytes and the integrity of the BSCB. In this study, we found that asiaticoside could inhibit the loss of junction proteins just 1 day after SCI in vivo, but our in vitro study showed no significant differences in the expression of endothelial junction proteins between the control and asiaticoside treatment groups. We also found that asiaticoside could inhibit endoplasmic reticulum (ER) stress and pericyte apoptosis, which might be associated with the inhibition of junction protein reduction in ECs. Thus, we investigated the interactions between pericytes and ECs. Our results showed that asiaticoside could decrease the release of matrix metalloproteinase (MMP)-9 in pericytes and therefore upregulate the expression of junction proteins in ECs. Furthermore, the protective effect of asiaticoside on pericytes is related to the inhibition of ER stress via the MAPK signaling pathway. Taken together, our results demonstrate that asiaticoside treatment inhibits BSCB disruption and enhances functional recovery after SCI.

Umbilical mesenchymal stem cell-derived exosomes promote spinal cord functional recovery through the miR-146b/TLR4 -mediated NF-κB p65 signaling pathway in rats

Spinal cord injury (SCI) is an incurable central nervous system impairment that lack of efficient treatment. Exosomes derived from mesenchymal stem cells (MSCs) are widely applied in disease treatment. This work aimed to determine the promising therapeutic effects of MSC-derived exosomal miRNA146b on SCI. A rat spinal cord injury (SCI) model and lipopolysaccharide (LPS)-induced PC12 cell model were established. Exosomes were extracted from human umbilical cord mesenchymal stem cells (hUCMSCs). The identification of exosomes was performed by using transmission electronic microscope (TEM) and nanoparticle tracking analysis (NTA). Hematoxylin and eosin (HE) staining and TUNEL assay were performed to assess tissue damage and apoptosis, respectively. ELISA was performed to detect levels of inflammatory cytokines. Cell viability was checked by cell counting kit 8 (CCK-8). Gene expression and protein levels were detected by qPCR and western blotting assay. The interaction between miR-146 b and Toll-like receptor 4 (TLR4) was assessed by luciferase reporter gene assay. The hUCMSC-derived exosomes could notably alleviate the spinal cord injury and cell apoptosis. The exosomal miR-146 b treatment suppressed the release of IL-1 β, IL-6, and TNFα. The miR-146 b suppressed the expression of TLR4, directly interact with the 3′-untranslated region (3′UTR) of TLR4, and inactivated the nuclear factor κB (NF-κB) signaling. The hUCMSCs-derived exosomal miR-146 b protects neurons from spinal cord injury through targeting the TLR4 and inactivating the NF-κB signaling. Our findings supported the application of hUCMSCs-derived exosomal miR-146 b for the protection of SCI.

Shenqisherong pill ameliorates neuronal apoptosis by inhibiting the JNK/caspase-3 signaling pathway in a rat model of cervical cord compression

Ethnopharmacological relevanceThe Shenqisherong (SQSR) pill is an empirical prescription of traditional Chinese medicine (TCM), which originated from the National Chinese Medical Science Master, Shi Qi. It has been widely used in the treatment of cervical spondylotic myelopathy (CSM) and promote the recovery of spinal cord function, but underlying molecular mechanism remains unclear. Aim of the studyThe objective of this study was to confirm the neuroprotective effects of the SQSR pill. Materials and methodsA rat model of chronic compression at double-level cervical cord was used in vivo. The protective role of SQSR pill on CSM rats was measured by Basso, Beattie, and Bresnahan (BBB) locomotor scale, inclined plane test, forelimb grip strength assessment, hindlimb pain threshold assessment, and gait analysis. The levels of reactive oxygen species (ROS) were examined by Dihydroethidium (DHE) staining and 2′,7′-Dichlorofluorescein (DCF) assay, and apoptosis was detected by TdT-mediated dUTP nick-end labeling (TUNEL) assay. The expression of apoptosis proteins was evaluated by immunofluorescence staining and Western blot. ResultsSQSR pill could facilitate locomotor function recovery in rats with chronic cervical cord compression, reduce local ROS in the spinal cord and downregulate the c-Jun-N-terminal kinase (JNK)/caspase-3 signaling pathway. In addition, the SQSR pill could protect primary rat cortical neurons from glutamate-treated toxicity in vitro by reducing the ROS and downregulating the phosphorylation of JNK and its downstream factors related to neuronal apoptosis meditated by the caspase cascade. Then, the neuroprotective effect was counteracted by a JNK activator. ConclusionsTogether, SQSR pill could ameliorate neuronal apoptosis by restraining ROS accumulation and inhibiting the JNK/caspase-3 signaling pathway, indicating that SQSR pill could be a candidate drug for CSM.

Curcumin-Containing polyphosphazene nanodrug for Anti-Inflammation and nerve regeneration to improve functional recovery after spinal cord injury

The microenvironment of excessive inflammation and the activation of apoptotic signals are primary barriers to neurological recovery following spinal cord injury (SCI). Thus, long-lasting anti-inflammation has become an effective strategy to navigate SCI. Herein, a curcumin (CUR)-containing nanosystem (FCTHPC) with high drug loading efficiency was reported via assembling hydrophobic CUR into cross-linked polyphosphazene (PPZ), and simultaneous loading and coordinating with porous bimetallic polymers for greatly enhanced the water-solubility and biocompatibility of CUR. The nanosystem is noncytotoxic when directing its biological activities. By inhibiting the expression of pro-inflammatory factors (IL-1β, TNF-α and IL-6) and apoptotic proteins (C-caspase-3 and Bax/Bcl-2), which may be accomplished by activating the Wnt/β-catenin pathway, the versatile FCTHPC can significantly alleviate the damage to tissues and cells caused by inflammation and apoptosis in the early stage of SCI. In addition, the long-term in vivo studies had demonstrated that FCTHPC could effectively inhibit the formation of glial scars, and simultaneously promote nerve regeneration and myelination, leading to significant recovery of spinal cord function. This study emphasises the promise of the biocompatible CUR-based nanosystem and provides a fresh approach to effectively treat SCI.

The circ_006573/miR-376b-3p Axis Advances Spinal Cord Functional Recovery after Injury by Modulating Vascular Regeneration.

Abnormal expression of non-coding RNAs after spinal cord injury (SCI) is associated with pathophysiological outcomes. We bioinformatically predicted a circRNA-miRNA-mRNA axis in SCI. A total of 4690 mRNAs, 17 miRNAs, and 3928 circRNAs were differentially expressed, with co-expressed RNAs predicted to regulate pathways related to wound healing. Among the most highly differentially expressed circRNAs, circ_006573, but not circ_016395, weakened the viability and migration of rat aortic endothelial cells, and its biological effects were rescued with miR-376b-3p mimics. Furthermore, circ_006573 overexpression induced changes in Cebpb, IL-18, and Plscr1 expression that were reversed by miR-376b-3p. In a rat model, circ_006573 shRNA administration improved the pathological manifestations of SCI and ameliorated motor function. Moreover, the expression of CD31, CD34, and VEGF-A in spinal cord tissues was significantly elevated after circ_006573 shRNA treatment, indicating that circ_006573 may be involved in vascular regeneration and functional recovery after SCI. Thus, the circ_006573-miR-376b-3p axis offers a foundation for understanding pathophysiological mechanisms and predicting strategies for treating SCI.

Treatment of rigid post-traumatic thoracolumbar kyphosis by a novel technique of spinal joints release

ObjectiveThe purpose of this study was to evaluate the feasibility of a novel technique named spinal joints release (SJR) and observe its efficacy in treating rigid post-traumatic thoracolumbar kyphosis (RPTK).MethodsRPTK patients who were treated by SJR with facet resection, limited laminotomy, clearance of the intervertebral space, and release of the anterior longitudinal ligament through the intervertebral foramen and disc of injury segment from August 2015 to August 2021 were reviewed. Intervertebral space release, internal fixation segment, operation time, and intraoperative blood loss were recorded. The intraoperative, postoperative, and final follow-up complications were observed. An improvement in the VAS score and ODI index was observed. Spinal cord functional recovery was evaluated by American Spinal Injury Association Impairment Scale (AIS). Improvement of local kyphosis (Cobb angle) was evaluated by radiography.ResultsForty-three patients were successfully treated by the SJR surgical technique. Open-wedge anterior intervertebral disc space was performed in 31 cases, and repeated release and dissection of the anterior longitudinal ligament and callus were performed in 12 cases. There was no lateral annulus fibrosis release in 11 cases, the anterior half release of lateral annulus fibrosis in 27 cases, and complete release in five cases. There were five cases of screw placement failure in one or two side pedicles of the injured vertebrae due to excessive resection of the facets and improper pre-bending of the rod. Sagittal displacement occurred in four cases at the released segment due to the complete release of bilateral lateral annulus fibrosus. Autologous granular bone + Cage was implanted in 32 cases, and autologous granular bone was implanted in 11 cases. There were no serious complications. The average operation time was 224 ± 31 min, and intraoperative blood loss was 450 ± 225 mL. All the patients were followed up with an average of 26 ± 8.5 months. The VAS scores and ODI index improved significantly at the final follow-up. All of the 17 patients with incomplete spinal cord injury achieved more than one grade of neurological recovery at the final follow-up. An 87% correction rate of kyphosis was achieved and maintained, with the Cobb angle decreasing from 27.7° preoperatively to 5.4° at the final follow-up.ConclusionPosterior SJR surgery for patients with RPTK has the advantages of less trauma and less blood loss, and kyphosis correction is satisfactory.

Retracted: lncRNA HOTAIR Inhibition by Regulating HMGB1/ROS/NF‐κB Signal Pathway Promotes the Recovery of Spinal Cord Function

Retracted: lncRNA HOTAIR Inhibition by Regulating HMGB1/ROS/NF‐<i>κ</i>B Signal Pathway Promotes the Recovery of Spinal Cord Function

Treating Pediatric Irreducible Atlantoaxial Rotatory Fixation (IAARF) by Unlocking Facet Joint Through Transoral Approach and Fixing With Slim-TARP Plate (15 Cases Series).

Irreducible atlantoaxial rotatory fixation (IAARF) often requires surgical treatment. Transoral unlocking the facet joints is a key measure for the treatment of IAARF. We investigate a novel method for treating pediatric IAARF by unlocking facet joint through transoral appraoch and fixed with slim-tarp plate in same stage with same approach. The objective of this study is to investigate the method and efficacy of a unique transoral approach to unlock facet joints and fixation with slim-shaped transoral anterior reduction plate (slim-TARP) plate in the treatment of IAARF. Fifteen patients diagnosed with AARF were transferred to our hospital. After 1 week of bidirectional cervical cranial traction, they were diagnosed with irreducible AARF that, and then underwent transoral release and fixation with slim-TARP plate procedures. Postoperative computed tomography and magnetic resonance were used to evaluate the reduction effect, bone fusion, and fusion time. Japanese orthopaedic association scores were used to compare the recovery of spinal cord function in patients before and after surgery. Complications such as wound infection, neurovascular injury, and loosening of internal fixation were evaluated too. All 15 patients underwent transoral unlocking facet joint and fixation with slim-TARP procedures smoothly. The operation time were 129.2±11.9 minutes, blood loose were 83±23 mL. There were no neurological injury, wound infections, verified or suspected vertebral artery injury, etc. All patients were followed up for a mean of 17.8±6.6 months (range: 12 to 36 mo). Bony fusion was achieved in all patients. Mean fusion time was 3.6±1.2 months (range: 3 to 6 mo). Complete correction of torticollis was achieved in all 15 cases. Preoperative symptoms of neck pain and limitation of neck movement were effectively alleviated at 3 months after surgery. The 3 patients with preoperative neurological deficits had significant relief after surgery, and their latest follow-up results showed that their Japanese orthopaedic association scores increased from 13.0±1.0 to 16.3±0.6. Transoral release and fixation with slim-TARP plate by transoral approach is a feasible and safe method for treating pediatric irreducible atlantoaxial rotatory fixation.

MiR-146a-5p-modified hUCMSC-derived exosomes facilitate spinal cord function recovery by targeting neurotoxic astrocytes

BackgroundAcute spinal cord injury (SCI) is a devastating result of neurological trauma with subsequent microenvironment dyshomeostasis that induces neurotoxic phenotype acquisition by astrocytes, exacerbating neurological function impairment. Exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) have demonstrated essential therapeutic effects after central nervous system trauma. However, whether hUCMSC-derived exosomes exert therapeutic effects on neurotoxic astrocytes to facilitate SCI function recovery remains unclear. Additionally, the limited efficiency of single exosomes may restrict the optimization of exosomal biological functions.MethodsWe first determined that exosomes reduce the deleterious effects of neurotoxic astrocytes in vitro and in vivo. Then, we identified critical functional microRNAs (miRNAs). miR-146a-5p was overexpressed in exosomes, and then, miR-146a-5p-modified exosomes were used to investigate the ability of exosomes to reduce neurotoxic astrocyte effects, preserve neurons and promote neurological function recovery in rats with SCI.ResultsCell counting kit-8 and neurite length analyses revealed that exosomes partially reduced the negative effects of neurotoxic astrocytes on PC12 cell viability and neurites in vitro. The exosomes also attenuated inflammatory responses, reduced the number of neurotoxic astrocytes and preserved neural tissue in rats with SCI. Immunofluorescence assays suggested that the number of neurotoxic astrocytes was rapidly increased by injury, reaching a peak 5 days post-injury (dpi) and returning to the normal level 14dpi. Exosomal miR-146a-5p was identified as the critical functional miRNA. Overexpression of miR-146a-5p in exosomes strengthened the biological function of the exosomes. Therefore, the modified exosomes exerted more powerful therapeutic effects than the unmodified exosomes, reducing the deleterious effects of neurotoxic astrocytes both in vitro and in vivo and promoting locomotor function of the hindlimbs in the rats with SCI. Through a series of gain- and loss-of-function experiments, Traf6 and Irak1 were identified as targets of exosomal miR-146a-5p. Ultimately, we found that miR-146a-5p-modified exosomes exerted their function by targeting Traf6/Irak1/NFκB pathway in neurotoxic astrocytes.ConclusionsIn summary, miR-146a-5p-modified exosomes exerted a more powerful effect than unmodified exosomes to promote neurological function recovery in rats with SCI by targeting neurotoxic astrocytes. Therefore, miR-146a-5p-modified exosomes are promising therapeutics for SCI.

N6-methyladenosine modification: A potential regulatory mechanism in spinal cord injury.

N6-methyladenosine (m6A), an essential post-transcriptional modification in eukaryotes, is closely related to the development of pathological processes in neurological diseases. Notably, spinal cord injury (SCI) is a serious traumatic disease of the central nervous system, with a complex pathological mechanism which is still not completely understood. Recent studies have found that m6A modification levels are changed after SCI, and m6A-related regulators are involved in the changes of the local spinal cord microenvironment after injury. However, research on the role of m6A modification in SCI is still in the early stages. This review discusses the latest progress in the dynamic regulation of m6A modification, including methyltransferases (“writers”), demethylases (“erasers”) and m6A -binding proteins (“readers”). And then analyses the pathological mechanism relationship between m6A and the microenvironment after SCI. The biological processes involved included cell death, axon regeneration, and scar formation, which provides new insight for future research on the role of m6A modification in SCI and the clinical transformation of strategies for promoting recovery of spinal cord function.

Early expansive single sided laminoplasty decompression treatment severe traumatic cervical spinal cord injury.

BackgroundSevere traumatic cervical spinal cord injury (tcSCI) is a disastrous event for patients and families. Maximizing spinal cord function recovery has become the primary therapeutic goal. This study investigated the effect of early extensive posterior decompression on spinal cord function improvement after severe tcSCI.MethodsA retrospective review of 83 consecutive patients who underwent extensive open-door laminoplasty decompression within 24 h after severe tcSCI (American Spinal Injury Association (ASIA) impairment scale (AIS) grade A to C) between 2009 and 2017 at our institution was performed. The patient clinical and demographic data were collected. Neurological functional recovery was evaluated according to the Japanese Orthopaedic Association (JOA) score system, ASIA motor score (AMS) and AIS grade.ResultsAmong the 83 patients initially included, the baseline AIS grade was A in 12, B in 28, and C in 43. Twenty-three patients (27.7%) had a high cervical injury. Cervical spinal stenosis (CSS) was identified in 37 patients (44.6%). The mean intramedullary lesion length was 59.6 ± 20.4 mm preoperatively and 34.2 ± 13.3 mm postoperatively (p < 0.0001). At the final follow-up visit, an improvement of at least one and two AIS grades was found in 75 (90.4%) and 41 (49.4%) patients, respectively. 24 (64.9%) patients with an improvement of least two AIS grades had CSS. The mean AMS and JOA score were significantly improved at discharge and the final follow-up visit compared with on admission (p < 0.0001).ConclusionsOur results suggest that early expansive laminoplasty decompression may improve neurological outcomes after severe tcSCI, especially in patients with CSS. Larger and prospective controlled studies are needed to validate these findings.