The involvement of epidural fat in ossification of the ligamentum flavum: From the perspective of exosomal proteome.

Ossification of the ligamentum flavum (OLF) is the primary etiology of thoracic spinal stenosis. The functional properties of epidural fat (EF), an adipose tissue located in close proximity to ligamentum flavum (LF), have been scarcely investigated. The metabolic state of adipocytes significantly influences their functionality, and exosomes play a pivotal role in intercellular communication. This study aimed to investigate the role of EF-derived exosomes in OLF and characterize their protein profile by proteomics analysis. Our findings demonstrate that exosomes obtained from EF adjacent to OLF possess the ability to enhance osteogenesis of fibroblasts in vitro. Furthermore, proteomics analysis revealed metabolic dysfunction in EF adipocytes and identified lactate dehydrogenase A (LDHA) as a potential mediator involved in the development of OLF. This study provides new insights into the pathogenic mechanism underlying OLF and offers a theoretical basis for preventing and treating ligament ossification.

Chiropractic management of lumbar spinal epidural lipomatosis in a U.S. Veterans Affairs clinic: a report of two cases.

Background: Spinal epidural lipomatosis (SEL) is a rare contributor of low back pain (LBP) that can present with or without radicular symptoms. Case Presentation: A 51-year-old and 65-year-old male presented with chronic LBP to the Veterans Affairs chiropractic clinic for a trial of care. One had a moderate degree of lumbar spinal stenosis with known SEL and the other had severe. The patient with moderate grade stenosis responded favorably with weeks of transient benefit after visits and the patient with severe grade did not find benefit with care. Summary: SEL is a condition that conservative care providers should be aware of as a potential cause of central canal stenosis or neuroforaminal narrowing. Chiropractic management of SEL has been scarcely reflected in the published literature, but may be a viable option for transient symptom management.

MRI parameters predict central lumbar spinal stenosis combined with redundant nerve roots: a prospective MRI study.

Background: To observe changes in the cauda equina nerve on lumbar MRI in patients with central lumbar spinal stenosis (LSS). Methods: 878 patients diagnosed with LSS by clinical and MRI were divided into the redundant group (204 patients) and the nonredundant group (674 patients) according to the presence or absence of redundant nerve roots (RNRs). The anteroposterior diameter of the spinal canal (APDS) and the presence of multiple level stenosis, disc herniation, thickening of ligamentum flavum (LF) and increased epidural fat were assessed on MRI. Univariate and multivariate logistic regression analyses were performed to explore the predictors of LSS combined with RNRs. Results: Patients with LSS combined with RNRs had thicker epidural fat, smaller APDS and more combined multifaceted stenosis. Female patients and older LSS patients were more likely to develop RNRs; there was no difference between two groups in terms of disc herniation (p > 0. 05). Age, APDS, multiple level stenosis, and increased epidural fat were significantly correlated with the formation of LSS combined with RNRs (p < 0.05). Conclusion: A smaller APDS and the presence of multiple level stenosis, thickening of LF, and increased epidural fat may be manifestations of anatomical differences in patients with LSS combined with RNRs. Age, APDS, multiple level stenosis, and increased epidural fat play important roles. The lumbar spine was measured and its anatomy was observed using multiple methods, and cauda equina changes were assessed to identify the best anatomical predictors and provide new therapeutic strategies for the management of LSS combined with RNRs.

Role of epidural fat in the local milieu: what we know and what we don't.

PURPOSE: Traditionally, the epidural fat (EF) is known as a physical buffer for the dural sac against the force and a lubricant facilitating the relative motion of the latter on the osseous spine. Along with the development of the studies on EF, controversies still exist on vital questions, such as the underlying mechanism of the spinal epidural lipomatosis. Meanwhile, the scattered and fragmented researches hinder the global insight into the seemingly dispensable tissue. METHODS: Herein, we reviewed literature on the EF and its derivatives to elucidate the dynamic change and complex function of EF in the local milieu, especially at the pathophysiological conditions. We start with an introduction to EF and the current pathogenic landscape, emphasizing the interlink between the EF and adjacent structures. We generally categorize the major pathological changes of the EF into hypertrophy, atrophy, and inflammation. RESULTS AND CONCLUSIONS: It is acknowledged that not only the EF (or its cellular components) may be influenced by various endogenic/exogenic and focal/systematic stimuli, but the adjacent structures can also in turn be affected by the EF, which may be a hidden pathogenic clue for specific spinal disease. Meanwhile, the unrevealed sections, which are also the directions the future research, are proposed according to the objective result and rational inference. Further effort should be taken to reveal the underlying mechanism and develop novel therapeutic pathways for the relevant diseases.

MR imaging differentiating features between lytic and degenerative lumbosacral spondylolisthesis.

Spondylolisthesis is characterized by the displacement of one vertebral body in relation to the adjacent vertebra. It is commonly observed in the lower lumbar region and can be caused by a variety of factors, including spondylolysis (a fracture in the pars interarticularis) or degenerative disease. Magnetic resonance imaging (MRI) is becoming increasingly popular as the primary modality for evaluation of low back pain and is often used in the absence of radiographs or Computed Tomography. However, it can be challenging for radiologists to differentiate between the two types of spondylolisthesis based on MRI alone. The goal of this article is to identify key imaging features on MRI that can aid radiologists in differentiating between spondylolysis and degenerative spondylolisthesis on MRI. Five key concepts are discussed: the "step-off" sign, the "wide canal" sign, T2 cortical bone signal on MRI, epidural fat interposition, and fluid in the facet joints. The utility, limitations and potential pitfalls of these concepts are also discussed to provide a comprehensive understanding of their use in differentiating between the two types of spondylolisthesis on MRI.

Prx1+ MPCs Accumulate in the Dura Mater of Wild-Type and p21-/- Mice Followed by a Specific Reduction in p21-/- Dural MPCs.

Epidural fat contains a population of mesenchymal progenitor cells (MPCs), and this study explores the behavior of these cells on the adjacent dura mater during growth and in response to injury in a p21 knockout mouse model. p21-/- mice are known to have increased cell proliferation and enhanced tissue regeneration post-injury. Therefore, it is hypothesized that the process by which epidural fat MPCs maintain the dura mater can be accelerated in p21-/- mice. Using a Prx1 lineage tracing mouse model, the epidural fat MPCs are found to increase in the dura mater over time in both C57BL/6 (p21+/+ ) and p21-/- mice; however, by 3 weeks post-tamoxifen induction, few MPCs are observed in p21-/- mice. These endogenous MPCs also localize to dural injuries in both mouse strains, with MPCs in p21-/- mice demonstrating increased proliferation. When epidural fat MPCs derived from p21-/- mice are transplanted into dural injuries in C57BL/6 mice, these MPCs are found in the injury site. It is demonstrated that epidural fat MPCs play a role in dural tissue maintenance and are able to directly contribute to dural injury repair. This suggests that these MPCs have the potential to treat injuries and/or pathologies in tissues surrounding the spinal cord.

Proteoglycan 4 is present within the dura mater and produced by mesenchymal progenitor cells.

Mesenchymal progenitor cells (MPCs) have been recently identified in human and murine epidural fat and have been hypothesized to contribute to the maintenance/repair/regeneration of the dura mater. MPCs can secrete proteoglycan 4 (PRG4/lubricin), and this protein can regulate tissue homeostasis through bio-lubrication and immunomodulatory functions. MPC lineage tracing reporter mice (Hic1) and human epidural fat MPCs were used to determine if PRG4 is expressed by these cells in vivo. PRG4 expression co-localized with Hic1+ MPCs in the dura throughout skeletal maturity and was localized adjacent to sites of dural injury. When Hic1+ MPCs were ablated, PRG4 expression was retained in the dura, yet when Prx1+ MPCs were ablated, PRG4 expression was completely lost. A number of cellular processes were impacted in human epidural fat MPCs treated with rhPRG4, and human MPCs contributed to the formation of epidural fat, and dura tissues were xenotransplanted into mouse dural injuries. We have shown that human and mouse MPCs in the epidural/dura microenvironment produce PRG4 and can contribute to dura homeostasis/repair/regeneration. Overall, these results suggest that these MPCs have biological significance within the dural microenvironment and that the role of PRG4 needs to be further elucidated.

Prx1 + and Hic1+ Mesenchymal Progenitors Are Present Within the Epidural Fat and Dura Mater and Participate in Dural Injury Repair.

Epidural fat is commonly discarded during spine surgery to increase the operational field. However, mesenchymal progenitor cells (MPCs) have now been identified in human epidural fat and within the murine dura mater. This led us to believe that epidural fat may regulate homeostasis and regeneration in the vertebral microenvironment. Using two MPC lineage tracing reporter mice (Prx1 and Hic1), not only have we found that epidural fat MPCs become incorporated in the dura mater over the course of normal skeletal maturation, but have also identified these cells as an endogenous source of repair and regeneration post-dural injury. Moreover, our results reveal a partial overlap between Prx1+ and Hic1+ populations, indicating a potential hierarchical relationship between the two MPC populations. This study effectively challenges the notion of epidural fat as an expendable tissue and mandates further research into its biological function and relevance.

Fibrotic and inflammatory characteristics of epidural fat adjacent to the ossification area in patients with ossification of the ligament flavum.

Objectives: To observe histological and inflammatory characteristics of epidural fat (EF) adjacent to the ossification area in patients with ossification of the thoracic ligament flavum (TOLF) and provide a preliminary research basis for investigating the impact of the EF on OLF. Methods: Samples of EF and autologous subcutaneous adipose tissue (SCAT) from TOLF patients (n = 26) and non-TOLF patients (n = 23) were harvested during posterior thoracic spine surgery. Adipocyte size and fibrosis were measured by histology. Vascularization and inflammatory cell infiltration were evaluated by immunohistochemical staining. Adipogenesis-related genes were assessed by real-time quantitative PCR. Conditioned media from cultured EF were evaluated via enzyme-linked immunosorbent assay to detect the secretion of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and leptin. The phosphorylated STAT3 protein level in ligament flavum (LF) was examined using Western blot. Results: Adipocytes size in EF was similar between in the TOLF and non-TOLF groups, but significantly smaller than that from autologous SCAT. Adipogenesis-related mRNA expression in EF was lower than that in SCAT. More fibrosis and vascularization were found in TOLF than in non-TOLF. EF in the TOLF group exhibited more macrophages and B lymphocytes infiltrated. The levels of cytokines such as IL-6, TNF-α, and leptin secreted by EF were significantly higher in the TOLF group than non-TOLF. The level of phosphorylated STAT3 in LF was significantly upregulated in the TOLF group. Conclusions: Morphologically, EF adjacent to the ossification area is smaller and more uniform than autologous SCAT, exhibiting a characteristic similarity to visceral fat. EF in the TOLF group shows a more fibrotic, vascularized, and inflammatory phenotype, which secretes multiple cytokines. The phosphorylated STAT3 protein was significantly upregulated in the TOLF group. Whether these properties of EF directly affect the process of OLF needs to be further explored.

Reconstruction of Epidural Fat to Prevent Epidural Fibrosis After Laminectomy in Rabbits.

Laminectomy can effectively decompress the spinal cord and expand the vertebral canal. However, the fibrosis that appears may cause adherence and recompression of the spinal cord or/and nerve root, which may cause failed back syndrome (FBS) and make the reexposure process more difficult. Reconstruction of the epidural fat may be an ideal method to achieve satisfactory results. Thirty-six New Zealand rabbits were randomly divided into three groups: control, extracellular matrix (ECM), and ECM+aMSCs groups. Saline, ECM gel, and ECM+aMSC complex were placed, respectively, at the fifth lumbar vertebrate of the rabbits. Epidural fat and fibrosis formation were detected by magnetic resonance imaging (MRI) and histologically at the 4th, 8th, and 12th weeks. Quantitative RT-PCR was used to detect the expression of interleukin 6 (IL-6) and transforming growth factor ß (TGF-ß). MRI and Oil Red O staining revealed epidural fat formation at the 12th week in the ECM+aMSCs group. Hematoxylin and eosin staining showed that the numbers of fibroblasts in the ECM gel and ECM+aMSCs groups were less than the control group at the 4th and 8th weeks (p < 0.05). Masson's trichrome staining showed that the proportion of collagen fibers in the ECM gel and ECM+aMSCs group was lower than the control group (p < 0.05). Quantitative RT-PCR showed the expressions of TGF-ß and IL-6 were lower in the ECM gel and ECM+aMSCs group than those in the control group (p < 0.05) at the 4th week, but higher at the 8th week. We successfully reconstructed the epidural fat with ECM gel and aMSC complex; additionally, IL-6 and TGF-ß cytokines were lower at early stage after laminectomy. Impact statement Our study revealed that epidural fat formed at the 12th week in the extracellular matrix (ECM) plus mesenchymal stem cell (MSC) group after laminectomy in rabbits; additionally, transforming growth factor ß (TGF-ß) (fibrosis) and interleukin 6 (IL-6) (inflammation) expression was reduced. Thus, we believe that our study makes a significant contribution to the literature because we were able to successfully reconstruct the epidural fat with an ECM gel combined with MSCs and reduce local inflammation.

Isolation and Characterization of Extracellular Vesicle from Mesenchymal Stem Cells of the Epidural Fat of the Spine.

STUDY DESIGN: An experimental study with extracellular vesicles (EVs) from mesenchymal stem cell (MSC) of the epidural fat (EF) of the spine. PURPOSE: This study aims to isolate the exosomes from epidural fat-derived mesenchymal stem cells (EF-MSCs) and fully characterize the EF-MSC-EVs. OVERVIEW OF LITERATURE: EF-MSCs were reported in 2019, and a few studies have shown the positive outcomes of using EF-MSCs to treat specific spine pathologies. However, MSCs have significant limitations for conducting basic studies or developing therapeutic agents. Although EVs are an emerging research topic, no studies have focused on EVs, especially exosomes, from EF and EF-MSCs. METHODS: In this study, we isolated the exosomes using the tangential flow filtration (TFF) system with exosome-depleted fetal bovine serum and performed the characterization tests via western blotting, reverse transcription-polymerase chain reaction, nanoparticle tracking analysis (NTA), and transmission electron microscopy. RESULTS: In transmission electron microscopy, the exosome had a diameter of approximately 100-200 nm and had a spherical shape, whereas in the NTA, the exosome had an average diameter of 142.8 nm with a concentration of 1.27×1010 particles/mL. The flow cytometry analysis showed the expression of CD63 and CD81. The western blotting analysis showed the positive markers. CONCLUSIONS: These findings showed that isolating the exosomes via TFF resulted in high-quality EF-MSC exosome yield. Further studies with exosomes from EF-MSC are needed to evaluate the function and role of the EF tissue.

Numerical Models of Spinal Cord Trauma: The Effect of Cerebrospinal Fluid Pressure and Epidural Fat on the Results.

Spinal cord injury (SCI) is commonly caused by traumatic mechanical damage. Although numerical models can help predict the mechanics of SCI without putting the subjects in danger, previous studies did not focus on alternations in cerebrospinal fluid (CSF) pressure and did not account for the presence of epidural fat. This study aims to numerically compare the mechanical behavior of the human spine when subjected to contusion and burst fracture with varying CSF pressure, either normal or elevated pressure that represents intracranial hypertension. An additional aim is to find out how the presence of the fat in the model affects the SCI calculations. CSF and epidural fat were modeled as smoothed-particle hydrodynamics (SPH) and the soft tissues were modeled as hyperelastic. This approach made it possible to account for CSF pressure alteration and its effect on the cord. Validation models resulted in good correlation with previous numerical and experimental studies. The results were able to capture the fluid dynamics of the CSF while demonstrating a considerable change in the stresses of the spinal cord. The comparison of the CSF pressures demonstrated that SCI in patients with elevated pressure and in regions where insufficient epidural fat exists might lead to higher spinal cord stresses. Yet, in regions with enough fat, the fat can absorb energy and counteract the effect of the elevated pressure. These results indicate important aspects that need to be accounted for in future numerical models of SCI while also demonstrating how the injury might be aggravated by preexisting conditions.

Comparisons of Extracellular Vesicles from Human Epidural Fat-Derived Mesenchymal Stem Cells and Fibroblast Cells.

Extracellular vesicles (EVs) are generated and secreted by cells into the circulatory system. Stem cell-derived EVs have a therapeutic effect similar to that of stem cells and are considered an alternative method for cell therapy. Accordingly, research on the characteristics of EVs is emerging. EVs were isolated from human epidural fat-derived mesenchymal stem cells (MSCs) and human fibroblast culture media by ultracentrifugation. The characterization of EVs involved the typical evaluation of cluster of differentiation (CD antigens) marker expression by fluorescence-activated cell sorting, size analysis with dynamic laser scattering, and morphology analysis with transmission electron microscopy. Lastly, the secreted levels of cytokines and chemokines in EVs were determined by a cytokine assay. The isolated EVs had a typical size of approximately 30-200 nm, and the surface proteins CD9 and CD81 were expressed on human epidural fat MSCs and human fibroblast cells. The secreted levels of cytokines and chemokines were compared between human epidural fat MSC-derived EVs and human fibroblast-derived EVs. Human epidural fat MSC-derived EVs showed anti-inflammatory effects and promoted macrophage polarization. In this study, we demonstrated for the first time that human epidural fat MSC-derived EVs exhibit inflammatory suppressive potency relative to human fibroblast-derived EVs, which may be useful for the treatment of inflammation-related diseases.

[Epidural lipomatosis : management proposal]. / Comment je traite la lipomatose épidurale.

Epidural lipomatosis is a rare condition characterized by excessive accumulation of normal fat in the epidural space. This paper presents the results of a retrospective study of the charts of 20 patients. The 20 patients - 17 men and 3 women - were on average 64 years old. They suffered from radiculopathy and/or neurogenic claudication. Lipomatosis was idiopathic in 6 patients and secondary in 14 patients. Lipomatosis was MRI grade 2 in 30 % of cases and grade 3 in 70 % of cases. The patients have all been improved thanks to decompressive surgery by laminectomy and resection of epidural fat. According to our experience and to the literature, surgical decompression is an effective and safe procedure for patients with symptomatic lumbar epidural lipomatosis in case of failure of conservative treatment or in case of neurological deficits. We present a decision tree that can help in the management of this disease.

La lipomatose épidurale est une affection rare caractérisée par une accumulation excessive de graisse normale dans l'espace épidural. Ce travail présente les résultats d'une étude rétrospective des dossiers de 20 patients. Les 20 patients, 17 hommes et 3 femmes, étaient âgés en moyenne de 64 ans. Ils souffraient d'une radiculopathie et/ou d'une claudication neurogène. La lipomatose était idiopathique chez 6 patients et secondaire chez 14 patients. L'IRM a démontré une lipomatose de grade 2 dans 30 % des cas et de grade 3 dans 70 % des cas. Les patients ont tous été améliorés grâce à la chirurgie de décompression par laminectomie et résection du tissu épidural. D'après notre expérience et selon la littérature, la décompression chirurgicale est une procédure efficace et sûre pour les patients présentant une lipomatose épidurale lombaire symptomatique en cas d'échec du traitement conservateur ou en cas de déficits neurologiques. Nous présentons un arbre décisionnel pouvant aider à la prise en charge de cette pathologie.

Epidural lipomatosis in elderly patient: A rare cause of cauda equina compression.

BACKGROUND: The most common cause of cauda equina compression in the elderly is lumbar spinal stenosis. Epidural lipomatosis is an additional known but rare cause of cauda equina compression readily diagnosed on MR studies. Notably, spinal canal decompression and direct excision of the epidural fat effectively manage this combined pathology. CASE DESCRIPTION: A 70-year-old male presented with progressive truncal obesity associated with refractory lumbar neurogenic claudication. The lumbar magnetic resonance imaging (MRI) showed excessive epidural fat extending from L4 to S2 resulting in thecal sac compression; this was confirmed on the MRI myelogram study. Following a decompressive laminectomy, the patient's cauda equina syndrome resolved. CONCLUSION: Recent weight gain with increased neurogenic claudication and the onset of a cauda equina syndrome may herald the presence of significant lumbar epidural lipomatosis. Here, laminectomy for excision of the excessive epidural fat resolved the patient's symptomatic spinal stenosis.

Clinical Implications of the Epidural Fat Thickness in the Management of Lumbar Spinal Stenosis.

OBJECTIVE: Lumbar epidural lipomatosis is a rare condition defined as the excessive accumulation of epidural fat (EF). We herein investigated the indicators of the posterior compression factors, EF and yellow ligament, to identify the clinical features of lumbar epidural lipomatosis. METHODS: Five hundred consecutive patients who underwent posterior lumbar decompression surgery for lumbar spinal stenosis (LSS) were retrospectively reviewed. The EF/SC-L index (the ratio of the anteroposterior length of the EF to that of the spinal canal [SC]) was evaluated at the spinal level that exhibited maximum dural tube compression. The participants were divided into 3 groups: grade I, EF/SC-L index ≤50%; grade II, EF/SC-L index 51%-74%; grade III, EF/SC-L index ≥75%. EF/SC-A (the ratio of the cross-sectional area of EF to that of SC) and YL/SC-A (the ratio of the cross-sectional area of yellow ligament [YL] to that of SC) were calculated. The clinical outcomes were assessed according to the Japan Orthopaedic Association scale for lumbar disease. RESULTS: EF/SC-L exhibited a significantly positive correlation with EF/SC-A (r = 0.82, P < 0.001), and a negative correlation with YL/SC-A (r = -0.71, P < 0.001). The Japan Orthopaedic Association score recovery rate was 56.7 ± 22.6 in the case-matched control group, 34.5 ± 31.2 in the grade II group (P < 0.001), and 39.6 ± 24.9 in the grade III group (P = 0.032). CONCLUSIONS: The EF/SC-L index is a simple and reliable indicator to quantitatively evaluate posterior compression in patients with LSS. As the accumulation of EF is associated with worse operative outcomes, the EF/SC-L index should be considered when planning lumbar decompression surgery for patients with LSS.

Epidural fat mesenchymal stem cells: Important microenvironmental regulators in health, disease, and regeneration: Do EF-MSCs play a role in dural homeostasis/maintenance?

Mesenchymal stem cells (MSCs) are present in fat tissues throughout the body, yet little is known regarding their biological role within epidural fat. We hypothesize that debridement of epidural fat and/or subsequent loss of MSCs within this tissue, disrupts homeostasis in the vertebral environment resulting in increased inflammation, fibrosis, and decreased neovascularization leading to poorer functional outcomes post-injury/operatively. Clinically, epidural fat is commonly considered a space-filling tissue with limited functionality and therefore typically discarded during surgery. However, the presence of MSCs within epidural fat suggests that itis more biologically active than historically believed and may contribute to the regulation of homeostasis and regeneration in the dural environment. While the current literature supports our hypothesis, it will require additional experimentation to determine if epidural fat is an endogenous driver of repair and regeneration and if so, this tissue should be minimally perturbed from its original location in the spinal canal. Also see the video abstract here https://youtu.be/MIol_IWK1os.

The impact of posterior epidural adipose tissue on postoperative outcomes after posterior decompression surgery for lumbar spinal stenosis: A prospectively randomized non-inferiority trial.

STUDY DESIGN: The present study is a prospectively randomized study. OBJECTIVE: The objective of the study was to evaluate the impact of posterior epidural adipose tissue (PAT) on postoperative outcome following lumbar decompression surgery for lumbar spinal stenosis (LSS) by whether PAT was removed or preserved during the surgical procedure. SUMMARY OF BACKGROUND DATA: In posterior decompression surgery for LSS, PAT is routinely removed without knowledge of its role and significance. However, considering adipose tissue has regenerative properties of damaged neighboring tissues or itself, PAT, which is adipose tissue located at peridural space, might also have a potential to regenerate the neighboring damaged tissue, including dura and nerve root in the lumbar spine, but this has not been thoroughly studied. METHODS: Of the 185 eligible patients screened for the current study, 181 patients were enrolled and randomly allocated into either group A (PAT removal, n = 90) or group B (PAT retention, n = 91). The primary outcome measure was pain intensity on the lower back and lower extremity. The secondary outcome measures were functional outcome based on the Oswestry disability index (ODI) and walking distance, complications during the surgical procedure, and surgical outcomes. RESULTS: Postoperative pain intensity on the lower back and lower extremity was greater in group A than in group B. Functional status on ODI and walking distance was also worse in group B than in group A (64.9% in group A and 66.2% in group B). The number of patients with aggravated pain intensity and deteriorated functional status in postoperative follow-up times was significantly greater in group A than in group B. There were no significant differences in surgical outcome and complications between the groups. CONCLUSION: Preserving epidural fat may be favorable in postoperative outcomes of posterior decompression surgery for LSS compared to removing epidural fat.

Extracellular Vesicles Derived from Epidural Fat-Mesenchymal Stem Cells Attenuate NLRP3 Inflammasome Activation and Improve Functional Recovery After Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating event which caused high mortality and morbidity. Recently, nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome has been showed to act a critical t role in the secondly injury phase of SCI. In current study, we aimed to investigate the effect and underlying molecular mechanisms of extracellular vesicles derived from epidural fat (EF)- mesenchymal stem cells (MSCs) for the treatment of SCI. Ninety-six Sprague-Dawley rats were used for current study and randomly divided into four groups: sham group, SCI group, SCI + Saline group, SCI + Extracellular vesicles group. Basso-Beattie-Bresnahan (BBB) scores was applied to evaluate the neurological functional recovery. Cresyl violet-stained was conducted evaluate the protective effect of EF-MSCs-Extracellular vesicles on lesion volume after SCI. ELISA, immunohistochemistry assay, TUNEL assay and western blotting were conducted to investigate the underlying molecular mechanisms. Our results demonstrated that the administration of EF-MSCs-Extracellular vesicles via tail vein injection improved neurological functional recovery and reduced the lesion volume after SCI. And systemic administration of EF-MSCs-Extracellular vesicles significantly inhibited NLRP3 inflammasome activation and reduced the expression of inflammatory cytokines. Additionally, the expression levels of proapoptotic protein Bax was decreased and antiapoptotic Bcl-2 was upregulated with the treatment of EF-MSCs-Extracellular vesicles after SCI. In summary, in current study, we demonstrated for the first time that the EF-MSCs-Extracellular vesicles can improve neurological functional recovery after SCI, and the underlying molecular mechanisms may partly through the inhibition of NLRP3 inflammasome activation.

Negative impact of spinal epidural lipomatosis on the surgical outcome of posterior lumbar spinous-splitting decompression surgery: a multicenter retrospective study.

BACKGROUND CONTEXT: Spinal epidural lipomatosis (SEL) results from excess lumbar epidural fat (EF) accumulation that compresses the cauda equina or nerve roots. Guidelines for the therapeutic management of SEL are not currently available. PURPOSE: To elucidate the efficacy of lumbar decompression surgery in SEL. STUDY DESIGN: Multicenter retrospective study. PATIENT SAMPLE: A total of 288 consecutive patients who underwent posterior lumbar spinous-splitting decompression surgery for lumbar spinal canal stenosis and followed up greater than 2 years at participating institutions were retrospectively reviewed. OUTCOME MEASURES: Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) and Roland-Morris Disability Questionnaire (RDQ). METHODS: Participants were divided into two groups according to the ratio of EF to anteroposterior diameter of the spinal canal (EF/SC-L) at the spinal level with maximum dural tube compression. Patients with EF/SC-L of ≥0.6 and <0.6 were defined as those with SEL and non-SEL, respectively. We assessed whether surgical treatment was "effective" or "not effective" using the JOABPEQ based on the following: an increase of ≥20 points in the postoperative score compared with the preoperative score, or a preoperative score <90 with a postoperative score ≥90 points. We constructed a multiple Poisson regression model by adjusting for confounding factors, and determined estimated relative risk (RR) for "not effective" with surgical treatment using the JOABPEQ. Additionally, we selected age-, sex-, BMI-, and decompression levels-matched patients with non-SEL and compared the frequency of "not effective" between SEL patients (n=60) and non-SEL patients (n=60). RESULTS: Analysis using the RDQ and JOABPEQ showed that the 1- and 2-year postoperative scores were significantly better than the preoperative scores in the both groups. Multivariable Poisson regression analysis demonstrated that SEL was significantly associated with "not effective" for decompression surgery in the 1-year postoperative outcomes of walking ability ([RR] 1.5, 95% confidence interval [CI] 1.0-2.2) and social life (RR 1.3, 95% CI 1.0-1.8) and the 2-year postoperative outcomes of walking ability (RR 1.6, 95% CI 1.2-2.3). Matching analysis showed that SEL was significantly associated with "not effective" with lumbar decompression surgery in the 2-year postoperative outcomes of walking ability (p=.02). CONCLUSIONS: Patients with SEL exhibited significant improvements in surgical outcomes at 1 and 2 years postoperatively. However, compared with the non-SEL group, the efficacy of posterior lumbar spinous-splitting decompression surgery was worse in the SEL group, especially for walking ability. These results indicate that EF accumulation should be considered when planning treatment for patients with lumbar spinal canal stenosis and estimating the efficacy of lumbar decompression surgery.