Recovery Of Spinal Cord Injury Research Articles

Fingolimod Nanoemulsions at Different Particle Sizes Define the Fate of Spinal Cord Injury Recovery.

Spinal cord injury (SCI) is a debilitating condition for which no definitive treatment has yet been identified. Notably, it influences other tissues through inflammatory reactions and metabolic disturbances. Therefore, fingolimod (FTY-720), as an FDA-approved inflammatory modulator, would be promising. In the present study, nanocarriers with two distinct monodisperse particle sizes of 60 (nF60) and 190 (nF190) nm were prepared via low-(stirring) and high-energy (probe ultrasound) emulsion oil in water (O/W) methods. Larger nanocarriers showed higher EE% and sustained-release profile than smaller nanocarriers. Neural stem cell (NSC) viability and lactate dehydrogenase (LDH) release were studied in the presence of nanocarriers and free FTY-720. The results indicated that nanocarriers and free FTY-720 enhanced NSC viability compared with the control group. However, nF190 induced significantly less cell membrane damage than nF60. Nanocarriers and free FTY-720 enhanced motor neuron recovery in SCI rats, while body weight and return to bladder reflux by nF190 were significantly higher than those in the nF60 group. Return to bladder reflux might be due to the role of FTY-720 in the regulation of detrusor muscle tone and preservation of the integrity of vessels by acting on endothelial cells. Moreover, nF190 gained higher soleus muscle weight than the free drugs; probably decreasing proinflammatory cytokines in the soleus diminishes muscular atrophy in SCI rats. In summary, it might be said that larger nanocarriers with sustained-release profile and less cell membrane damage seem to be more efficient than smaller ones to manage SCI and enhance bladder reflux. These data will help pharmaceutical companies select the correct particle size for nanodrugs and develop more efficient drug formulations to treat SCI.

Enhanced effect of combining bone marrow mesenchymal stem cells (BMMSCs) and pulsed electromagnetic fields (PEMF) to promote recovery after spinal cord injury in mice.

Spinal cord injury (SCI) is a destructive traumatic disease of the central nervous system without satisfying therapy efficiency. Bone marrow mesenchymal stem cells (BMMSCs) therapy promotes the neurotrophic factors’ secretion and axonal regeneration, thereby promoting recovery of SCI. Pulsed electromagnetic fields (PEMF) therapy has been proven to promote neural growth and regeneration. Both BMMSCs and PEMF have shown curative effects for SCI; PEMF can further promote stem cell differentiation. Thus, we explored the combined effects of BMMSCs and PEMF and the potential interaction between these two therapies in SCI. Compared with the SCI control, BMMSCs, and PEMF groups, the combinational therapy displayed the best therapeutic effect. Combinational therapy increased the expression levels of nutritional factors including brain‐derived neurotrophic factor (BDNF), nerve growth factors (NGF) and vascular endothelial growth factor (VEGF), enhanced neuron preservation (NeuN and NF‐200), and increased axonal growth (MBP and myelin sheath). Additionally, PEMF promoted the expression levels of BDNF and VEGF in BMMSCs via Wnt/β‐catenin signaling pathway. In summary, the combined therapy of BMMSCs and PEMF displayed a more satisfactory effect than BMMSCs and PEMF therapy alone, indicating a promising application of combined therapy for the therapy of SCI.

Biocompatible exosome-modified fibrin gel accelerates the recovery of spinal cord injury by VGF-mediated oligodendrogenesis

Exosomes show potential for treating patients with spinal cord injury (SCI) in clinical practice, but the underlying repair mechanisms remain poorly understood, and biological scaffolds available for clinical transplantation of exosomes have yet to be explored. In the present study, we demonstrated the novel function of Gel-Exo (exosomes encapsulated in fibrin gel) in promoting behavioural and electrophysiological performance in mice with SCI, and the upregulated neural marker expression in the lesion site suggested enhanced neurogenesis by Gel-Exo. According to the RNA-seq results, Vgf (nerve growth factor inducible) was the key regulator through which Gel-Exo accelerated recovery from SCI. VGF is related to myelination and oligodendrocyte development according to previous reports. Furthermore, we found that VGF was abundant in exosomes, and Gel-Exo-treated mice with high VGF expression indeed showed increased oligodendrogenesis. VGF was also shown to promote oligodendrogenesis both in vitro and in vivo, and lentivirus-mediated VGF overexpression in the lesion site showed reparative effects equal to those of Gel-Exo treatment in vivo. These results suggest that Gel-Exo can thus be used as a biocompatible material for SCI repair, in which VGF-mediated oligodendrogenesis is the vital mechanism for functional recovery.

Extracellular Vesicles in the Pathogenesis, Treatment, and Diagnosis of Spinal Cord Injury: A Mini-Review.

Benefiting from in-depth research into stem cells, extracellular vesicles (EVs), which are byproducts of cells and membrane-wrapped microvesicles (30-120 nm) containing lipids, proteins, and nucleic acids, may cast light on the research and development of therapeutics capable of improving the neurological recovery of spinal cord injury (SCI) animals. However, the mechanistic modes of action for EVs in alleviating the lesion size of SCI remain to be solved, thus presenting a tremendous gap existing in translation from the laboratory to the clinic. The purpose of this minireview was to cover a wide range of basic views on EVs involved in SCI treatment, including the effects of EVs on the pathogenesis, treatment, and diagnosis of spinal cord injury. We searched databases (i.e., PubMed, Web of Science, Scopus, Medline, and EMBASE) and acquired all accessible articles published in the English language within five years. Studies reporting laboratory applications of EVs in the treatment of SCI were included and screened to include studies presenting relevant molecular mechanisms. This review first summarized the basic role of EVs in cell communication, cell death, inflammatory cascades, scar formation, neuronal regrowth, and angiogenesis after SCI, thereby providing insights into neuroprotection and consolidated theories for future clinical application of EVs. EVs participate in an extremely wide range of cell activities, play a critical role in cell communication centring neurons, and are considered potential therapies and biomarkers for SCI. miRNAs are the most abundant nucleic acids shipped by EVs and effluent cytokines, and they may represent important messengers of EVs and important factors in SCI treatment.

Resveratrol suppresses microglial activation and promotes functional recovery of traumatic spinal cord via improving intestinal microbiota

Spinal cord injury (SCI) can change the intestinal microbiota pattern and corresponding metabolites, which in turn affect the prognosis of SCI. Among many metabolites, short-chain fatty acids (SCFAs) are critical for neurological recovery after SCI. Recent research has shown that resveratrol exerts anti-inflammatory properties. But it is unknown if the anti-inflammatory properties of resveratrol are associated with intestinal microbiota and metabolites. We thus investigate the alteration in gut microbiota and the consequent change of SCFAs following resveratrol treatment. The SCI mouse models with retention of gut microbiota (donor) and depletion of gut microbiota (recipient) were established. Fecal microbiota transplantation from donors to recipients was performed with intragastrical administration. Spinal cord tissues of mice were examined by H&E, Nissl, and immunofluorescence stainings. The expressions of the inflammatory profile were examined by qPCR and cytometric bead array. Fecal samples of mice were collected and analyzed with 16S rRNA sequencing. The results showed that resveratrol inhibited the microglial activation and promoted the functional recovery of SCI. The analysis of intestinal microbiota and metabolites indicated that SCI caused dysbiosis and the decrease in butyrate, while resveratrol restored microbiota pattern, reversed intestinal dysbiosis, and increased the concentration of butyrate. Both fecal supernatants from resveratrol-treated donors and butyrate suppressed the expression of pro-inflammatory genes in BV2 microglia. Our result demonstrated that fecal microbiota transplantation from resveratrol-treated donors had beneficial effects on the functional recovery of SCI. One mechanism of resveratrol effects was to restore the disrupted gut microbiota and butyrate.

Aggressive piecemeal excision and cervical bridging fixation for cervical vertebral osteosarcoma in two dogs and two cats

AbstractTwo dogs and two cats were referred for primary osteosarcoma of the cervical vertebrae. Each case was treated surgically with a combination of aggressive tumour resection and bridging fixation of the vertebrae, which was performed cranial and caudal to the affected site, using metal implants and polymethylmethacrylate. The cervical spines were stabilised by spinal reconstruction, and the tumours were extensively removed. Aggressive resection and spinal reconstruction prevented pathological fractures, contributed to spinal cord injury recovery, improved clinical symptoms and prolonged life expectancy.

Microglia coordinate cellular interactions during spinal cord repair in mice

Traumatic spinal cord injury (SCI) triggers a neuro-inflammatory response dominated by tissue-resident microglia and monocyte derived macrophages (MDMs). Since activated microglia and MDMs are morphologically identical and express similar phenotypic markers in vivo, identifying injury responses specifically coordinated by microglia has historically been challenging. Here, we pharmacologically depleted microglia and use anatomical, histopathological, tract tracing, bulk and single cell RNA sequencing to reveal the cellular and molecular responses to SCI controlled by microglia. We show that microglia are vital for SCI recovery and coordinate injury responses in CNS-resident glia and infiltrating leukocytes. Depleting microglia exacerbates tissue damage and worsens functional recovery. Conversely, restoring select microglia-dependent signaling axes, identified through sequencing data, in microglia depleted mice prevents secondary damage and promotes recovery. Additional bioinformatics analyses reveal that optimal repair after SCI might be achieved by co-opting key ligand-receptor interactions between microglia, astrocytes and MDMs.

Spinal cord decellularized matrix scaffold loaded with engineered basic fibroblast growth factor-overexpressed human umbilical cord mesenchymal stromal cells promoted the recovery of spinal cord injury.

Spinal cord injury (SCI) will lead to irreversible damage of sensory and motor function of central nervous system, which seriously affects patient's quality of life. A variety of nerve engineering materials carrying various stem cells and cell growth factors had used to promote the repair of SCI, but they could not mimic the actual matric niche at spinal cord to promote cell proliferation and differentiation. Thus, developing novel biomaterial providing better niche of spinal cord is a new strategy to treat the severe SCI. In this study, we constructed porcine spinal cord decellularized matrix scaffold (SC-DM) with biocompatibility to load engineered basic fibroblast growth factor-overexpressing human umbilical cord mesenchymal stromal cells (bFGF-HUCMSCs) for treating SCI. The continuously released bioactive bFGF factors from grafted bFGF-HUCMSCs and three-dimensional niche by SC-DM promoted the differentiation of endogenous stem cells into neurons with nerve conduction function, leading a markedly motor function recovery of SCI. These results indicated that the functional bFGF-HUCMSCs/SC-DM scaffold provided more suitable matric niche for nerve cells, that would be a promising strategy for the clinical application of SCI.

Warm acupuncture therapy alleviates neuronal apoptosis after spinal cord injury via inhibition of the ERK signaling pathway

Purpose Warm acupuncture (WA) therapy has been applied to treat spinal cord injury (SCI), but the underlying mechanism is unclear. The current study attempted to explore the WA therapy on neuronal apoptosis of SCI and the relationship with the extracellular signal-regulated kinase (ERK) signaling pathway. Methods The rat SCI models were established by the impact method. SCI rat models were subjected to WA treatment at Dazhui (GV14) and Jiaji points (T10), Yaoyangguan (GV3), Zusanli (ST36), and Ciliao (BL32). The rat SCI models were established by the impact method. WA and U0126 treatments were performed on the SCI rats. Motor function and neuronal apoptosis were detected. The relative mRNA of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), the phosphorylation level of ERK 1/2 and levels of B-cell lymphoma-2 (Bcl-2), BCL2-Associated X (Bax), and caspase-3 in spinal cord tissue were tested. Results After WA treatment, the Basso, Beattie & Bresnahan locomotor rating scale (BBB scale) of SCI rats in the WA treatment was significantly raised from 7 to 14 days after SCI. WA and U0126 treatment significantly diminished apoptotic cells and preserved the neurons in the injured spinal cord. WA and U0126 treatment alleviated the production of inflammatory cytokines in the spinal cord. The distinct increase of p-ERK 1/2 induced by SCI was reversed in WA and U0126 treatment groups. WA and U0126 treatment augmented the level of Bcl-2 and reversed the elevated cleaved caspase-3 protein level after SCI. Conclusion Our study demonstrated that WA might be associated with the downregulation of the ERK signaling pathway. In summary, our findings indicated that WA promotes the recovery of SCI via the protection of nerve cells and the prevention of apoptosis. Meanwhile, the anti-apoptotic effect of WA might be associated with the downregulation of the ERK signaling pathway, which could be one of the mechanisms of WA in the treatment of SCI.

Clemastine Promotes Differentiation of Oligodendrocyte Progenitor Cells Through the Activation of ERK1/2 via Muscarinic Receptors After Spinal Cord Injury.

The recovery of spinal cord injury (SCI) is closely associated with the obstruction of oligodendrocyte progenitor cell (OPC) differentiation, which ultimately induces the inability to generate newly formed myelin. To address the concern, drug-based methods may be the most practical and feasible way, possibly applying to clinical therapies for patients with SCI. In our previous study, we found that clemastine treatment preserves myelin integrity, decreases the loss of axons, and improves functional recovery in the SCI model. Clemastine acts as an antagonist of the muscarinic acetylcholine receptor (muscarinic receptor, MR) identified from a string of anti-muscarinic drugs that can enhance oligodendrocyte differentiation and myelin wrapping. However, the effects of clemastine on OPC differentiation through MRs in SCI and the underlying mechanism remain unclear. To explore the possibility, a rat model of SCI was established. To investigate if clemastine could promote the differentiation of OPCs in SCI via MR, the expressions of OPC and mature OL were detected at 7 days post injury (dpi) or at 14 dpi. The significant effect of clemastine on encouraging OPC differentiation was revealed at 14 dpi rather than 7 dpi. Under pre-treatment with the MR agonist cevimeline, the positive role of clemastine on OPC differentiation was partially disrupted. Further studies indicated that clemastine increased the phosphorylation level of extracellular signal–regulated kinase 1/2 (p-ERK1/2) and the expressions of transcription factors, Myrf and Olig2. To determine the relationship among clemastine, ERK1/2 signaling, specified transcription factors, and OPC differentiation, the ERK1/2 signaling was disturbed by U0126. The inhibition of ERK1/2 in SCI rats treated with clemastine decreased the expressions of p-ERK 1/2, Myrf, Olig2, and mature OLs, suggesting that ERK1/2 is required for clemastine on promoting OPC differentiation and that specified transcription factors may be affected by the activity of ERK1/2. Moreover, the impact of clemastine on modulating the level of p-ERK 1/2 was restricted following cevimeline pre-injecting, which provides further evidence that the role of clemastine was mediated by MRs. Altogether, our data demonstrated that clemastine, mediated by MRs, promotes OPC differentiation under the enhancement of Myrf and Olig2 by activating ERK1/2 signaling and suggests a novel therapeutic prospect for SCI recovery.

Biofabricated Nano-Cerium Oxide Loaded Polycaprolactone with Resveratrol Improves Repair of Spinal Cord Injury Through the PTEN/AKT Pathway

Spinal cord injury (SCI) is the main cause of severe dysfunction of limbs, causes serious physical and psychological damage to patients. Resveratrol (RVL) has been proven to improve the function of damaged organs, therefore we tried to explore whether RVL could exert a protective effect on SCI, as well as its related mechanism. Emulsion/solvent evaporation method was used to prepare CeO2-loaded microspheres and RVL nanopreparations, and bio fabricated CeO2-RVL/PCL was developed and assessed by Fourier Transform Infrared Spectroscopy (FTIR), scanning electron microscope (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) analysis. Then, the therapeutic effect of newly prepared CeO2-RVL/PCL on SCI was evaluated by assays. Bio fabricated CeO2-PCL/RVL was successfully established with good biocompatibility and stability. The CeO2-PCL/RVL effectively reduced apoptosis and spinal cord water content, and promoted the recovery of SCI in mice. Importantly, neuroprotective effect of CeO2-PCL/RVL on SCI was highly correlated with activation of the PTEN/AKT pathway. Our study successfully developed the biofabricated nano-CeO2 loaded PCL polymer, which proved that the CeO2-PCL/RVL is a feasible medical material for relieving SCI. The neuroprotective effect of CeO2-PCL/RVL on SCI relied on activation of the PTEN/AKT pathway. This study is expected to provide new ideas on treatment of SCI.

Collagen scaffold loaded allogeneic neural stem cells promoted locomotion recovery of spinal cord injury mainly through secreting neurotrophic factors

The combination of biological scaffold and neural stem cells (NSCs) is a promising treatment strategy for spinal cord injury (SCI). But adverse niche at injures spinal cord severe hamper the transplanted NSCs to preferentially differentiate neurons. In this study, we compared the therapeutic outcomes in rat completely transected SCI model after transplantations of collagen scaffold loaded with NSCs in different forms including unicellular NSCs, neurospheres, differentiated unicellular NSCs, and differentiated neurospheres. The results showed collagen scaffold combined each form of NSCs could markedly restore the motor function of the hindlimbs by Basso-Beattie-Bresnahan(BBB) scoring to similar levels. The transcriptome analysis showed there were similar expressions of neurotrophic factors among neurospheres, differentiated unicellular NSCs, and differentiated neurospere. Next, we enriched neurotrophic factors secreted from culture medium of these three forms of NSCs respectively and combined with collagen scaffold were transplanted into SCI to further assay therapeutic effects of secreting neurotrophic factors on SCI. BBB score analysis showed that the secreted neurotrophic factors from above three forms of NSCs had similar functional recovery of SCI. Therefore, we proposed that allogeneic NSCs transplant promotes functional recovery of SCI predominantly by secreting neurotrophic factors, not by direct neuronal replacement of differentiated neurons from transplanted cells.

LncRNA MIAT Promotes Spinal Cord Injury Recovery in Rats by Regulating RBFOX2-Mediated Alternative Splicing of MCL-1.

LncRNA myocardial infarction-associated transcript (MIAT) alleviates acute spinal cord injury (ASCI)-induced neuronal cell apoptosis, but the specific mechanism of it involved in regulating SCI progression needs further exploration. Here, a SCI rat model was established, followed by administration with adenovirus-mediated MIAT overexpression vector (Ad-MIAT) alone or together with Ad-RBFOX2 (RNA binding fox-1 homolog 2). The data indicated that MIAT overexpression promoted motor function recovery, improved morphology of injured tissues, and restrained neuron loss and cell apoptosis in SCI rats. Then, PC-12 cells were treated with H2O2 to induce cell injury. And highly expressed MIAT suppressed H2O2-caused decrease in cell viability and increase in cell apoptosis. MIAT stabilized RBFOX2 protein expression by binding to RBFOX2, thereby promoting RBFOX2-induced upregulation of anti-apoptotic MCL-1L (myeloid cell leukemia sequence 1) and reduction of pro-apoptotic MCL-1S. And silencing RBFOX2 in vitro blocked the inhibitory effect of MIAT on cell apoptosis. Moreover, MCL-1-specific steric-blocking oligonucleotides (SBOs) were used to transfer the MCL-1 pre-mRNA splicing pattern from MCL-1L to MCL-1S. SBOs reversed the protection effect of RBFOX2 overexpression on H2O2-induced cell injury. Furthermore, overexpression of MCL-1L instead of MCL-1S facilitated autophagy activation in H2O2-stimulated cells. Interestingly, co-overexpression of MIAT and RBFOX2 had a better promoting effect on SCI recovery. In conclusion, MIAT mitigated SCI by promoting RBFOX2-mediated alternative splicing of MCL-1. Our findings might provide a promising therapeutic target for SCI.

Strategies for Biomaterial-Based Spinal Cord Injury Repair via the TLR4-NF-κB Signaling Pathway.

The repair and motor functional recovery after spinal cord injury (SCI) has remained a clinical challenge. Injury-induced gliosis and inflammation lead to a physical barrier and an extremely inhibitory microenvironment, which in turn hinders the recovery of SCI. TLR4-NF-κB is a classic implant-related innate immunomodulation signaling pathway and part of numerous biomaterial-based treatment strategies for SCI. Numerous experimental studies have demonstrated that the regulation of TLR4-NF-κB signaling pathway plays an important role in the alleviation of inflammatory responses, the modulation of autophagy, apoptosis and ferroptosis, and the enhancement of anti-oxidative effect post-SCI. An increasing number of novel biomaterials have been fabricated as scaffolds and carriers, loaded with phytochemicals and drugs, to inhibit the progression of SCI through regulation of TLR4-NF-κB. This review summarizes the empirical strategies for the recovery after SCI through individual or composite biomaterials that mediate the TLR4-NF-κB signaling pathway.

Injection of Cerium Oxide Nanoparticles to Treat Spinal Cord Injury in Rats.

This study investigated the effects of local injection of cerium oxide nanoparticles (CeONPs) in a rat spinal cord injury (SCI) model. Thirty-six adult male Wistar rats were divided into 4 groups: controls (healthy animals), sham (laminectomy), SCI (laminectomy+SCI induction), and treatment (laminectomy+SCI induction+intrathecal injection of CeONPs immediately after injury). SCI was induced using an aneurysm clip at the T12-T13 vertebral region. Motor performance and pain threshold tests were performed weekly; H&E staining and measurement of cavity sizes were performed 6 weeks after injury. The expression of granulocyte colony-stimulating factor (GCSF), P44/42 MAPK, P-P44/42 MAPK, Tau, myelin-associated glycoprotein(MAG) was evaluated after 6 weeks by Western blot. The Basso, Beattie, and Bresnahan locomotor scoring scales improved in animals receiving CeONPs compared with SCI animals. The cavity sizes were less in the treatment group. GCSF expression was similar in the animals receiving CeONPs compared with the SCI group but the expression of ERK1/ERK2 and phospho-ERK was lower than in the SCI group. Expression levels of Tau and MAG were significantly increased in treated animals compared to the SCI group. These data indicate that the use of CeONPs may improve motor functional recovery in SCI.

Stimulation Parameters Used During Repetitive Transcranial Magnetic Stimulation for Motor Recovery and Corticospinal Excitability Modulation in SCI: A Scoping Review.

There is a growing interest in non-invasive stimulation interventions as treatment strategies to improve functional outcomes and recovery after spinal cord injury (SCI). Repetitive transcranial magnetic stimulation (rTMS) is a neuromodulatory intervention which has the potential to reinforce the residual spinal and supraspinal pathways and induce plasticity. Recent reviews have highlighted the therapeutic potential and the beneficial effects of rTMS on motor function, spasticity, and corticospinal excitability modulation in SCI individuals. For this scoping review, we focus on the stimulation parameters used in 20 rTMS protocols. We extracted the rTMS parameters from 16 published rTMS studies involving SCI individuals and were able to infer preliminary associations between specific parameters and the effects observed. Future investigations will need to consider timing, intervention duration and dosage (in terms of number of sessions and number of pulses) that may depend on the stage, the level, and the severity of the injury. There is a need for more real vs. sham rTMS studies, reporting similar designs with sufficient information for replication, to achieve a significant level of evidence regarding the use of rTMS in SCI.

Mechanism Underlying Acupuncture Therapy in Spinal Cord Injury: A Narrative Overview of Preclinical Studies

Spinal cord injury (SCI) results from various pathogenic factors that destroy the normal structure and function of the spinal cord, subsequently causing sensory, motor, and autonomic nerve dysfunction. SCI is one of the most common causes of disability and death globally. It leads to severe physical and mental injury to patients and causes a substantial economic burden on families and the society. The pathological changes and underlying mechanisms within SCI involve oxidative stress, apoptosis, inflammation, etc. As a traditional therapy, acupuncture has a positive effect promoting the recovery of SCI. Acupuncture-induced neuroprotection includes several mechanisms such as reducing oxidative stress, inhibiting the inflammatory response and neuronal apoptosis, alleviating glial scar formation, promoting neural stem cell differentiation, and improving microcirculation within the injured area. Therefore, the recent studies exploring the mechanism of acupuncture therapy in SCI will help provide a theoretical basis for applying acupuncture and seeking a better treatment target and acupuncture approach for SCI patients.

EFFECTS OF EXTRACELLULAR VESICLES ISOLATED FROM SUBVENTRICULAR ZONE ON MOLECULAR CHANGES FOLLOWING SPINAL CORD INJURY ON WISTAR RATS

Spinal cord injury (SCI) may occur as a result of traumatic crash to the spine that dislocates one or many vertebrae. SCI has two events to bring about the injury in the spinal cord that result at the end it will lead to bad consequences and loss of neurons; SCI complications are general loss of motor and sensory function. Extracellular vesicles (EVs) are very small vesicles produced by cells that contribute to cell to cell communication, transferring bioactive lipids, proteins, RNA. The aim of this research is to determine the effect of EVs on inflammasomes complex after SCI on rats. EVs were harvested characterized and cultured as exosomes, the animals are divided to 5 groups: control, sham, vehicle, SCI + treatment, SCI + EVs group. Spinal cord injury was induced using weight compression. 10 μl of EVs were injected intrathecally into lumber cistern in a space between L4-L5 laminae slowly. Gene expression of Caspase-1, ASC and NLRP3 were determined by RT-PCR. Western blot for determining the protein content of the inflammasomes were carried out. SCI up regulated the level of inflammasome complex both mRNA and proteins. Inthrathecal injection of EVs down regulated the inflammasome complex and make neuronal recovery. SCI can up regulate the level of inflammasome complex both mRNA and proteins. EVs are good therapeutic agent for SCI and increase neuronal recovery, inthrathecal injection is the best method of injection MSCs for treatment of SCI.

AuNPs@PDA-PLGA nanomembrane combined with electrical stimulation promotes spinal cord injury recovery

Electroconductive biomaterials combined with bioelectrical stimulation as a treatment for nerve injury has attracted extensive attention in recent years. This study investigated the effect of AuNPs@PDA-PLGA nanomembrane combined with electrical stimulation (ES) on promoting functional recovery of spinal cord injury (SCI). In this study, an AuNPs@PDA-PLGA was prepared and its characterization and biological properties were determined by means of scanning electron microscope (SEM), atomic force microscope (AFM) and X-ray diffraction (XRD). The effects of AuNPs@PDA-PLGA nanomembranes combined with ES on NSCs were evaluated in vitro. Finally, BBB score and immunohistochemical staining were used to confirm the therapeutic effect of AuNPs@PDA-PLGA nanomembrane combined with ES on recovery of SCI. The results showed that AuNPs@PDA-PLGA nanomembrane had good property for NSCs growth. Nanomembrane combined with ES could effectively promote the proliferation and differentiation of NSCs. Animal experiments results showed that the combination of AuNPs@PDA-PLGA nanomembrane and ES could promote the regeneration of new neurons and the formation of neuronal synapses, thus decrease cavity area, which all contribute to the functional recovery of spinal cord injury. Our results suggest that AuNPs@PDA-PLGA nanomembrane combined with ES can effectively promote functional recovery of SCI and provide a promising therapeutic option for SCI treatment.

Navigating Neurological Recovery with NeuroAiD in Severe Spinal Cord Injury: A Noteworthy Novelty?

Background and aim: NeuroAiD is a Chinese medicinal supplement containing nine herbal ingredients. Besides neuroprotection, NeuroAiD also promotes neuroregeneration. These have been extensively investigated both in vivo and in vitro. It has gained favour, especially amongst stroke and traumatic brain injury populations, to facilitate neuro recovery. To our knowledge, the SATURN study by Kumar et al. is the only study that has shifted the focus of NeuroAiD usage to the spinal cord injury (SCI) population. We present a case of complete tetraplegia who regained some neurological recovery following NeuroAiD supplementation. Methods: A 34-year-old police officer was involved in a helicopter crash in February 2020. He sustained a C6 vertebra burst fracture with severe spinal canal stenosis, C5 and C7 vertebrae fracture, and extensive cord oedema from C4 till T1, resulting in C4 AIS A Tetraplegia. Surgical fixation was performed on day 3. Upon admission to the rehabilitation ward at the end of March 2020, the best sensory level was C4, best motor C5, and total motor score 12. He regained some recovery throughout the stay, although he remained as C4 AIS A until discharged in April 2020. He started taking 2 capsules of NeuroAiD three times daily in May 2020 for six months. We followed him up until 1-year post-event to monitor his response. Results: The best sensory level improved to C5 at six months and C6 at 1-year, whilst the best motor level improved to C6 at six months and 1-year. The total motor score increased to 17 at six months and subsequently 22 at 1-year post-event. Overall, the neurological level of injury improved from C4 at three months to C5 at six months and C6 at 1-year post-event. AIS classification, however, remained A. Conclusion: The promising role of NeuroAiD in promoting neuro recovery in SCI is noteworthy for further exploration and investigation.