Treatment Of Spinal Cord Injury Research Articles

Electroacupuncture reduces neuronal apoptosis in rats with spinal cord injury by regulating GSK-3β expression and its phosphorylation

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. 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 1st, 7th, 14th, 21th and 28th 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. 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. 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.

Electroacupuncture of "Jiaji" (EX-B2) inhibits inflammatory response by regulating HMGB1/TLR4/NF-κB signaling pathway in rats with spinal cord injury

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. 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. 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). 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.

Amplification of Metalloregulatory Proteins in Macrophages by Bioactive ZnMn@SF Hydrogels for Spinal Cord Injury Repair.

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 Zn2+ and Mn2+ effectively suppressed M1 polarization. Based on these findings, mildly alkaline ZnMn-based layered double hydroxides (ZnMn-LDHs) self-assembled from Zn2+ coordinated with Mn2+ 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.

Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury

Applications of Regenerative Tissue-Engineered Scaffolds for Treatment of Spinal Cord Injury

Borneol-Functionalized Macrophage Membrane-Encapsulated Mesoporous Selenium Nanoparticles Loaded with Resveratrol for the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a serious neurological disease that can result in paralysis. After SCI occurs, the blood-spinal cord barrier (BSCB) is disrupted, and permeability is transiently elevated. However, the permeability of the BSCB returns to normal over time, which prevents many drugs from being used in subsequent treatments. In this study, we designed a borneol-functionalized macrophage membrane encapsulating mesoporous selenium nanoparticles loaded with resveratrol (MSe-Res-BMMs) for SCI treatment. In vivo animal experiments and in vitro cell experiments demonstrated that MSe-Res-BMMs were able to protect neurons from ferroptosis by reducing ROS levels and increasing glutathione peroxidase-4 (GPx-4) activity. In addition, this treatment also reduced ROS-induced inflammation and apoptosis by decreasing the expression of inflammatory factor IL-1β and apoptotic factor Cleaved Caspase-3 at the site of injury. Therefore, MSe-Res-BMMs are expected to provide new therapeutic options for SCI treatment.

Test Smart, Treat Smart-using clinician feedback to adapt a catheter-associated urinary tract infection intervention for spinal cord injury.

Catheter-associated urinary tract infection (CAUTI) prevention is a major target for hospital quality metrics because it is linked to increased morbidity, mortality, and health care costs. Health care systems use strict protocols surrounding catheterization and maintenance, which often disregard the clinical needs of special populations (eg, spinal cord injury [SCI]). However, for populations that rely on chronic instrumentation of the bladder, asymptomatic (ie, nonpathogenic) bacterial colonization in the bladder is common but not linked to adverse outcomes. Additionally, alterations in neurologic and sensory function after SCI make it difficult for clinicians to discern asymptomatic bacteriuria from acute urinary tract infection requiring antibiotics. Institutional policies for screening urine during SCI annual exams often lead to detection of bacteriuria but create a clinical decision-making challenge when determining whether antibiotic treatment is appropriate. To conduct preimplementation SCI-focused adaptations to the evidence-based practice (EBP) "Kicking CAUTI"-to develop a guide for SCI providers surrounding testing and treatment of CAUTI. Four 1-hour focus groups were conducted with SCI clinicians (prescribers and nursing staff) to assess insights on needed modifications to adapt Kicking CAUTI for SCI. The Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS) was used to plan and report adaptations in this work and the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to guide adaptation of the EBP for the SCI population. Content and thematic analysis guided our process. The clinical algorithm was simplified, a urinary symptom assessment added, and provider- and patient-facing educational materials were developed to support implementation efforts to create the Test Smart Treat Smart Intervention. Traditional CAUTI protocols do not adequately address the needs of those with SCI and modifications are needed. Provider feedback provides valuable insights when adapting population appropriate interventions.

Time to Surgery Following Complete Cervical Spinal Cord Injury: Evolution of Clinical Practice Patterns Over a Decade from 2010 to 2020 Across North American Trauma Centers.

This study aims to quantify the change in time to surgery for treatment of complete traumatic cervical spinal cord injury (SCI) patients in American College of Surgeons accredited trauma centers across North America over the last decade (2010-2020). This multi-center retrospective observational cohort study used data from the Trauma Quality Improvement Program from 2010 to 2020. All surgically treated patients with complete traumatic cervical SCI were included. Primary outcome was time to spine surgery from treating hospital arrival in hours. Both descriptive statistics and a multi-variable Poisson regression model clustering standard of errors by each included trauma center were used to evaluate and quantify the annual change in time to surgical intervention. The study included 6855 complete traumatic cervical SCI patients managed across 484 trauma centers in North America. Median time to spine surgery was 14.6 h. A total of 4618 patients (67.3%) underwent surgical intervention within 24 h from hospital arrival. From 2010 to 2020, median time to surgery decreased by an average 0.6 h (±0.15) per year. A multi-variable adjusted model for time to surgery demonstrated a significant downward annual reduction of 5% in time to surgery between the years 2010 and 2020 (Incidence rate ratio = 0.95; 95% Confidence Interval: 0.93-0.96). This study provides compelling real-world based quantification of the change in time to surgical intervention following traumatic cervical SCI. A significant decreasing annual trend pertaining to surgical timing across trauma centers in North America over the past decade was demonstrated.

ScRNA-Seq reveals age-dependent microglial evolution as a determinant of immune response following spinal cord injury

Spinal cord injury (SCI) is a debilitating condition of the central nervous system (CNS) that leads to severe impairments in sensory and motor functions. Previous studies have pointed out that patient age is a critical factor influencing SCI prognosis. However, the role of microglia in age-related differences in SCI outcomes remains unclear. The current study aims to identify specific microglial subtypes and investigate their responses and functional differences in SCI recovery across different age groups. Single-cell RNA sequencing (scRNA-seq) data were obtained from the Gene Expression Omnibus (GEO) database, integrating multiple datasets to identify microglial subtypes. We performed pseudotime trajectory analysis and cell-cell communication analysis to understand microglial differentiation and interactions. Finally, immunofluorescence staining of mouse model samples was conducted to validate our bioinformatics findings. Microglia were classified into four subtypes: Homeostatic, Proliferating, Inflammatory A, and Inflammatory B. The Young SCI group exhibited a higher proportion of Homeostatic microglia and Inflammatory microglia A, whereas the old SCI group had more Inflammatory Microglia B but lacked Homeostatic Microglia. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that markers for homeostasis microglia were enriched in immune modulation pathways. While makers for Inflammatory Microglia were enriched in immune response pathways. Specifically, markers for Inflammatory microglia B were enriched in pathways associated with overactive immune response. Pseudotime analysis indicated that microglia in young mice predominantly differentiated into Inflammatory Microglia A and Homeostatic Microglia, whereas in old mice, they tended to only differentiate into Inflammatory Microglia B. CellChat analysis showed increased pro-inflammatory signaling generated by Inflammatory Microglia B, exclusively in the old group. Our study demonstrates significant differences in microglial subtypes and functions between different age groups following SCI. These findings provide novel insights into the development of age-related therapeutic strategies and microglia-targeted biological treatments for SCI.

Macrophage membrane-mediated targeted curcumin biomimetic nanoparticles delivery for diagnosis and treatment of spinal cord injury by suppressing neuroinflammation and ferroptosis

Spinal cord injury (SCI) is a severe and debilitating central nervous system disorder characterized by permanent motor and sensory deficits, with limited effective treatment options available. Recent advancements have been made in the functionalization of biomimetic surfaces of nanoparticles through the incorporation of synthetic bionic and naturally derived cell membranes. One emerging strategy involves integrating biomimetic features into therapeutic agents to achieve low immunogenicity, high targeting specificity, and prolonged drug half-life. In this study, we detail the preparation of nanoparticles via the self-assembly of the amphiphilic diblock copolymer PEG-b-PHPMA with curcumin and PCPDTBT in water, followed by macrophage cell membrane coating using an extrusion method, resulting in the formation of stable curcumin-loaded nanoparticles coated with cell membrane (MM@Cur). Our experimental results demonstrate that MM@Cur treatment specifically targets the SCI site, effectively mitigates ferroptosis and central inflammation in a mouse model featuring spinal cord contusion, and enhances the recovery of the motor function of hind limbs post-SCI. Therefore, our findings highlight MM@Cur as a highly targeted biomimetic nanoparticle possessing potent anti-ferroptosis and anti-inflammatory properties, offering a promising therapeutic approach for the restoration of hind limb function post-spinal cord injury.

Mechanism of effect and therapeutic potential of NLRP3 inflammasome in spinal cord injury.

Spinal cord injury (SCI) is a serious and disabling central nervous system injury that can trigger various neuropathological conditions, resulting in neuronal damage and release of various pro-inflammatory mediators, leading to neurological dysfunction. Currently, surgical decompression, drugs and rehabilitation are primarily used to relieve symptoms and improve endogenous repair mechanisms; however, they cannot directly promote nerve regeneration and functional recovery. SCI can be divided into primary and secondary injuries. Secondary injury is key to determining the severity of injury, whereas inflammation and cell death are important pathological mechanisms in the process of secondary SCI. The activation of the inflammasome complex is thought to be a necessary step in neuro-inflammation and a key trigger for neuronal death. The NLRP3 inflammasome is a cytoplasmic multiprotein complex that is considered an important factor in the development of SCI. Once the NLRP3 inflammasome is activated after SCI, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Inhibition of inflammasomes can effectively inhibit inflammation and cell death in the body and promote the recovery of nerve function after SCI. Therefore, inhibition of NLRP3 inflammasome activation may be a promising approach for the treatment of SCI. In this review, we describe the current understanding of NLRP3 inflammasome activation in SCI pathogenesis and its subsequent impact on SCI and summarize drugs and other potential inhibitors based on NLRP3 inflammasome regulation. The objective of this study was to emphasize the role of the NLRP3 inflammasome in SCI, and provide a new therapeutic strategy and theoretical basis for targeting the NLRP3 inflammasome as a therapy for SCI.

Restorative Treatments for Cervical Spinal Cord Injury, a Narrative Review.

A narrative review. To summarize relevant data from representative studies investigating upper limb restorative therapies for cervical spinal cord injury. 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. 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. 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. 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.

Biomaterial-mediated delivery of traditional Chinese medicine ingredients for spinal cord injury: a systematic review.

Biomaterials loaded with ingredients derived from traditional Chinese medicine (TCM) are viewed as a promising strategy for treating spinal cord injury (SCI). However, a comprehensive analysis of the existing literature on this topic has not yet been conducted. Therefore, this paper systematically reviews researches related to this approach, aiming to identify gaps and shortcomings in the field. PubMed, EMBASE, Web of Science, Chinese Biomedical Literature, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched for retrieving studies on biomaterials loaded with TCM ingredients published from their inception to October 2024. Two reviewers performed screening of search results, information extraction, and literature quality assessment independently. For this systematic review, 41 publications were included. Six TCM ingredients-paclitaxel, curcumin, tetramethylpyrazine, resveratrol, berberine, and tanshinone IIA were combined with biomaterials for treatment of SCI. Biomaterials were categorized into hydrogels, biodegradable scaffolds, nanoparticles, and microspheres according to the type of scaffold. These drug delivery systems exhibit commendable biocompatibility, drug-loading capacity, and drug-release capabilities, and in combination with TCM ingredients, synergistically contribute to anti-oxidative stress, anti-inflammatory, neuroprotective, and anti-apoptotic effects. These studies demonstrated the efficacy of biomaterials loaded with TCM ingredients in facilitating motor function recovery and neuroprotection in SCI rats, providing evidence for future research. However, in the complex microenvironment of SCI, achieving the maximum drug loading capacity of TCM ingredients within biomaterials, along with sustained and controlled release to fully exert their pharmacological effects, remains a major challenge for future research. https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42024505000.

Microenvironment Self-Adaptive Nanomedicine Promotes Spinal Cord Repair by Suppressing Inflammation Cascade and Neural Apoptosis.

Despite various biomaterial-based strategies are tried in spinal cord injury (SCI), developing safe and effective microinvasive pharmacotherapy strategies is still an unmet clinical need. Stimuli-responsive nanomedicine has emerged as a promising non-invasion technology, which enhances drug delivery and promotes functional recovery following SCI. Considering the multiple progressive pathological events and the blood spinal cord barrier (BSCB) associating SCI, a microenvironment self-adaptive nanoparticle (custom-designed with rabies virus glycoprotein 29-RVG29 and hyaluronic acid-HA, RHNP) capable of consistently crossing the BSCB and selectively targeting inflammatory cells and neural cells based on different stages of SCI are developed. The data indicated that RHNP can effectively traverse the BSCB through RVG29, and adaptively modulate cellular internalization by selectively exposing either HA or RVG29 through diselenide bonds, depending on pathological reactive oxygen species (ROS) signals. Furthermore, curcumin is loaded into RHNP (RHNP-Cur) to improve motor function and coordination of hind-limbs in a traumatic SCI mouse model. This study finds that RHNP-Cur exhibited inhibitory effects on the inflammatory cascade originating from M1 microglia/macrophages and neurotoxic astrocytes, and protected neural cells from inflammation-induced apoptosis during nerve regeneration. Collectively, the work provides a microenvironment self-adaptive nanomedicine which enables efficient microinvasive treatment of SCI.

ACY1215 Exerts Anti-inflammatory Effects by Inhibition of NF-κB and STAT3 Signaling Pathway to Repair Spinal Cord Injury.

Spinal cord injury (SCI), a public health problem caused by mechanical injury, leads to secondary excessive inflammatory reactions and long-term damage to neurological function. ACY1215 is a highly selective histone deacetylase 6 (HDAC6) inhibitor and reportedly has anti-inflammatory effects; however, its regulatory role in SCI has not been studied. The purpose of this study was to explore the role of ACY1215 in preventing inflammation, inhibiting astrogliosis, enhancing remyelination and preserving axons after spinal cord injury and further exploring the possible cellular signaling pathways involved. First, lipopolysaccharide (LPS) was utilized to stimulate rat astrocytes in vitro. Quantitative RT (qRT)-PCR and Western blotting showed that ACY1215 inhibited the expression of glial fibrillary acidic protein (GFAP), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNFα) in LPS-activated astrocytes. In addition, Western blotting results showed that ACY1215 could inhibit the signal transduction pathway of nuclear factor-κB (NF-κB) and signal transducer and activator of transcription 3 (STAT3). In vivo, ACY1215 could exert anti-inflammatory effects by inhibiting the expression of inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Moreover, ACY1215 repaired spinal cord injury by reducing the formation of glial scars and promoting remyelination and nerve recovery. In summary, ACY1215 can inhibit the NF-κB and STAT3 signaling pathways in astrocytes, reduce inflammation and ameliorate SCI. Our results provide a novel strategy for the treatment of SCI.

Synergistic effects of human umbilical cord mesenchymal stem cells/neural stem cells and epidural electrical stimulation on spinal cord injury rehabilitation

Spinal cord injury (SCI) is a severe neurological condition marked by a complex pathology leading to irreversible functional loss, which current treatments fail to improve. Epidural electrical stimulation (EES) shows promise in alleviating pathological pain, regulating hemodynamic disturbances, and enhancing motor function by modulating residual interneurons in the lower spinal cord. Cell transplantation (CT), especially using human umbilical cord mesenchymal stem cells (hUCMSCs) and neural stem cells (NSCs), has significantly improved sensory and motor recovery in SCI. However, the limitations of single treatments have driven the exploration of a multifaceted strategy, combining various modalities to optimize recovery at different stages. To comprehensively investigate the effectiveness of in situ transplantation of hUCMSCs/NSCs combined with subacute epidural electrical stimulation in a murine spinal cord crush injury model, providing valuable references for future animal studies and clinical research. In this study, we first examined neural stem cell changes via mRNA sequencing in an in vitro Transwell co-culture model. We then explored cell interaction mechanisms using proliferation assays, differentiation assays, and neuron complexity analysis. For animal experiments, 40 C57BL/6 mice were assigned to four groups (Injury/EES/CT/Combination). Histological evaluations employed HE and immunofluorescence staining, while electrophysiological and behavioral tests assessed motor recovery. Quantitative data were reported as mean ± standard error, with statistical analyses performed using GraphPad Prism and SPSS. Initially, we found that NSCs in the in vitro co-culture model showed a unique expression profile of differentially expressed genes (DEGs) compared to controls. GO/KEGG analysis indicated these DEGs were mainly linked to cell differentiation and growth factor secretion pathways. Neuronal and astrocytic markers further confirmed enhanced NSC differentiation and neuronal maturation in the co-culture model. In vivo, live imaging and human nuclei immunofluorescence staining revealed that transplanted cells persisted for some time post-transplantation. Histological analysis showed that during acute inflammation, both the stem cell and combined therapy groups significantly inhibited microglial polarization. In the chronic phase, these groups reduced fibrotic scar formation and encouraged astrocytic bridging. Behavioral tests, including swimming and gait analysis, demonstrated that combined CT and EES therapy was more effective than either treatment alone. In summary, the combined therapy offers a promising approach for spinal cord injury treatment, providing superior outcomes over individual treatments. Our findings underscore the potential of a combined treatment approach utilizing stem cells transplantation and EES as an effective strategy for the comprehensive management of spinal cord crush injury in mice. This integrated approach holds promise for enhancing functional recovery and improving the quality of life for individuals with spinal cord injury (SCI).

Comparison of the long-term efficacy of ROI-C and conventional cage-plate in treatment of spinal cord injury without fracture or dislocation: a retrospective study

BackgroundThe self-locking cage (ROI-C, LDR, Troyes, France) has been clinically applied in the treatment of cervical degenerative disc disease (CDDD). However, only a few long-term clinical and radiographic studies have been conducted on the treatment of spinal cord injury without fracture or dislocation (SCIWFD) so far. A comparison between ACDF with either ROI-C or CCP was performed to determine the better treatment for SCIWFD.MethodsA total of 83 patients who underwent ACDF using either ROI-C or CCP were reviewed for radiological and clinical outcomes. The cohort comprised 60 males and 23 females, aged between 32 and 88 years old, with an average age of 58.23 years. All patients exhibited symptoms of nerve injury, including limb numbness, muscle weakness, hypoesthesia or urinary dysfunction. The preoperative ASIA classification of spinal nerve function: 7 cases of grade A, 23 cases of grade B, 34 cases of grade C and 19 cases of grade D were included in the study.ResultsA total of 48 patients underwent ACDF with ROI-C, while 35 patients received a conventional cage-plate. They were studied with a follow-up of 28.63 ± 17.41 months and 29.48 ± 15.43 months respectively. No significant difference was found in blood loss, JOA and ASIA between the two groups. No significant difference was found in cervical lordosis (CL) (P > 0.05). However, statistical difference was found in disc height of fused segment and T1 slope between the two groups (P < 0.05). No statistical difference was in the incidence of cage subsidence (P > 0.05). There was significant difference in the incidence of dysphagia. Both of two groups achieved bony fusion at final follow-up.ConclusionOur study demonstrated that ROI-C has the same efficacy as CCP in improving the cervical stability in treatment of SCIWFD. The migration of cage didn’t occur in ROI-C group at final follow-up, showing steadily fixed in cervical column. Moreover, the ROI-C does have the advantages of good therapeutic effect, mis-invasive, shorter operation time and fewer complications.

Curcumin/pEGCG-encapsulated nanoparticles enhance spinal cord injury recovery by regulating CD74 to alleviate oxidative stress and inflammation

Spinal cord injury (SCI) often accompanies impairment of motor function, yet there is currently no highly effective treatment method specifically for this condition. Oxidative stress and inflammation are pivotal factors contributing to severe neurological deficits after SCI. In this study, a type of curcumin (Cur) nanoparticle (HA-CurNPs) was developed to address this challenge by alleviating oxidative stress and inflammation. Through non-covalent interactions, curcumin (Cur) and poly (-)-epigallocatechin-3-gallate (pEGCG) are co-encapsulated within hyaluronic acid (HA), resulting in nanoparticles termed HA-CurNPs. These nanoparticles gradually release curcumin and pEGCG at the SCI site. The released pEGCG and curcumin not only scavenge reactive oxygen species (ROS) and prevents apoptosis, thereby improving the neuronal microenvironment, but also regulate CD74 to promote microglial polarization toward an M2 phenotype, and inhibits M1 polarization, thereby suppressing the inflammatory response and fostering neuronal regeneration. Moreover, in vivo experiments on SCI mice demonstrate that HA-CurNPs effectively protect neuronal cells and myelin, reduce glial scar formation, thereby facilitating the repair of damaged spinal cord tissues, restoring electrical signaling at the injury site, and improving motor functions. Overall, this study demonstrates that HA-CurNPs significantly reduce oxidative stress and inflammation following SCI, markedly improving motor function in SCI mice. This provides a promising therapeutic approach for the treatment of SCI.

Low-Energy extracorporeal shockwave therapy improves locomotor functions, tissue regeneration and modulating the inflammation induced FGF1 and FGF2 signaling to protect damaged tissue in spinal cord injury of rat model: An experimental animal study.

Spinal cord injury (SCI) is a debilitating condition that results in severe motor function impairments. Current therapeutic options remain limited, underscoring the need for novel treatments. Extracorporeal shockwave therapy (ESWT) has emerged as a promising noninvasive approach for treating musculoskeletal disorders and nerve regeneration. This study explored the effects of low-energy ESWT on locomotor function, tissue regeneration, inflammation, and mitochondrial function in a rat SCI model. Experiments were performed using locomotor function assays, CatWalk gait analysis, histopathological examination, immunohistochemical and immunofluorescence staining. The findings demonstrated that low-energy ESWT had a dose-dependent effect, with three treatment sessions (ESWT3) showing superior outcomes compared to a single session. ESWT3 significantly improved motor functions (run patterns, run average speed, and maximum variation, as well as the Basso, Beattie, and Bresnahan (BBB) score) and promoted tissue regeneration while reducing inflammation. ESWT3 significantly decreased levels of IL-1β, IL6 and macrophages (CD68) while increasing leucocyte (CD45) infiltration. Additionally, ESWT3 upregulated NueN and mitofusin 2 (MFN2), suggesting enhanced neuronal health and mitochondrial function. Moreover, ESWT3 modulated the expression of fibroblast growth factor 1 (FGF1), FGF2, their receptor FGFR1 and phosphorylation of ERK, aiding tissue repair and regeneration in SCI. This study highlights the potential of low-energy ESWT as an effective noninvasive treatment for SCI, demonstrating significant improvements in motor recovery, tissue regeneration, anti-inflammatory effects, and mitochondrial protection. These findings provide valuable insights into the mechanisms of ESWT and its therapeutic application for SCI recovery.

Falcarindiol improves functional recovery and alleviates neuroinflammation after spinal cord injury by inhibiting STAT/MAPK signaling pathways

Spinal cord injury (SCI) is a devastating trauma in the central nervous system (CNS), leading to motor and sensory impairment. Neuroinflammation is one of the critical contributors to the progression of secondary injury. Falcarindiol has been reported to efficaciously mitigate lipopolysaccharide (LPS)-mediated inflammation in RAW 264.7 cells. The role of falcarindiol in SCI recovery remains unclear. In this present study, traumatic SCI mice models and LPS-stimulated murine microglia cell line (BV2 cells) were performed to explore the pharmacological effects and the underlying mechanisms of falcarindiol in improving SCI repair with detection of motor function recovery, morphological changes, numbers of survival neurons and protein expression levels of inflammation or apoptosis-related proteins. Our study found that falcarindiol intervention could promote motor function recovery and reduce spinal cord tissue damage in mice following SCI. Mechanistically, falcarindiol intervention suppressed apoptosis-driven neuronal cell death and mitigated inflammatory reactions following SCI. Additionally, falcarindiol inhibited the activation of signal transducer and activator of transcription (STAT) and mitogen-activated protein kinases (MAPK) signaling pathways in vivo and in vitro. This suppression of STAT and MAPK activation by falcarindiol was reversed by STAT3 agonist Colivelin TFA and MAPK agonist C16-PAF in BV2 cells, respectively. Moreover, the study further demonstrated that the anti-inflammation role of falcarindiol was obstructed by Colivelin TFA but not by C16-PAF in LPS-stimulated BV2 cells, suggesting that falcarindiol may efficaciously ameliorate neuroinflammation through inhibiting the activation of STAT signaling pathway following SCI. Collectively, our study indicates that falcarindiol may be a novel drug candidate for the treatment and management of SCI.

Apelin regulates mitochondrial dynamics by inhibiting Mst1-JNK-Drp1 signaling pathway to reduce neuronal apoptosis after spinal cord injury

In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injury. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial fission, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis in PC12 cells. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial fission, improve antioxidant capacity, increase ATP production, decrease apoptosis, promote spinal cord morphological repair, maintain the number of nissl bodies, and enhance signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.