RESUMEN
Epidural adhesion or epidural fibrosis is the major reason for postoperative pain, which remains a clinically challenging problem. Current physical barriers fail to provide a satisfactory therapeutic outcome mainly due to their lack of adhesion, inability to prevent fluid leakage, and exhibiting limited antioxidant properties. Herein, we fabricated a cysteine-modified bioadhesive (SECAgel) with improved sealing and antioxidant properties for epidural adhesion prevention, inspired by the organism's antioxidant systems. The resulting SECAgel showed good injectability and in situ adhesion ability, effectively covering every corner of the irregular wound. Besides, it possessed efficient sealing properties (395.2 mmHg), effectively stopping blood leakage in the rabbit carotid artery transection model. The antioxidant experiments demonstrated that the SECAgel effectively scavenged various radicals and saved the cells from oxidative stress. Two animal models were used to show that the SECAgel effectively inhibited adhesion in both situations with and without cerebrospinal fluid leakage. The RNA sequencing analysis showed that SECAgel treatment effectively inhibited the expression of key genes related to adhesion development, inflammatory response, and oxidative stress. The SECAgel, together with good biocompatibility, can be a good candidate for preventing epidural adhesion in the clinic.
Asunto(s)
Antioxidantes , Animales , Conejos , Antioxidantes/farmacología , Antioxidantes/química , Adherencias Tisulares/prevención & control , Espacio Epidural/patología , Espacio Epidural/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Cisteína/química , Cisteína/farmacología , Humanos , Ratones , Adhesivos/química , Adhesivos/farmacología , MasculinoRESUMEN
Chronic inflammatory lesions (CIL) in the body are rare and inflammatory pseudotumor (IPT) is a subtype of CIL. Spine is an uncommon location of CIL, with most cases reported in the thoracic spine. Our objective was to review the current literature on IPT. To the best of our knowledge only about 13 cases are reported till date. A retrospective review of 13 existing cases was done. The etiopathogenesis of CIL is uncertain and total surgical excision remains the mainstay. It's a diagnosis of exclusion after ruling out commonly found lesions, both clinically and radiologically. Only histopathology can confirm the diagnosis. Total surgical resection remains the mainstay of treatment with adjuvant treatment only if there is a residue or a recurrence. CILs are rare lesions in the body with IPT being the commonest. Surgical excision remains the mainstay of treatment and a long-term follow up is warranted.
Asunto(s)
Vértebras Torácicas , Humanos , Vértebras Torácicas/patología , Vértebras Torácicas/diagnóstico por imagen , Vértebras Torácicas/cirugía , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/cirugía , Granuloma de Células Plasmáticas/patología , Granuloma de Células Plasmáticas/diagnóstico por imagen , Femenino , Masculino , Espacio Epidural/patología , Espacio Epidural/diagnóstico por imagen , Adulto , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
Low back pain due to epidural fibrosis is a major complication after spine surgery. Macrophages infiltrate the wound area post laminectomy, but the role of macrophages in epidural fibrosis remains largely elusive. In a mouse model of laminectomy, macrophage depletion decreased epidural fibrosis. CD146, an adhesion molecule involved in cell migration, is expressed by macrophages. CD146-defective macrophages exhibited impaired migration, which was mediated by reduced expression of CCR2 and suppression of the MAPK/ERK signaling pathway. CD146-defective macrophages suppress the MAPK/ERK signaling pathway by increasing Erdr1. In vivo, CD146 deficiency decreased macrophage infiltration and reduced extracellular matrix deposition in wound tissues. Moreover, the anti-CD146 antibody AA98 suppressed macrophage infiltration and epidural fibrosis. Taken together, these findings demonstrated that CD146 deficiency alleviates epidural fibrosis by decreasing the migration of macrophages via the Erdr1/ERK/CCR2 pathway. Blocking CD146 and macrophage infiltration may help alleviate epidural fibrosis.
Asunto(s)
Antígeno CD146 , Fibrosis , Macrófagos , Ratones Endogámicos C57BL , Receptores CCR2 , Animales , Receptores CCR2/metabolismo , Receptores CCR2/genética , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Antígeno CD146/metabolismo , Antígeno CD146/genética , Movimiento Celular , Ratones Noqueados , Espacio Epidural/patología , Masculino , Sistema de Señalización de MAP Quinasas/inmunología , Laminectomía , Modelos Animales de Enfermedad , Transducción de Señal , HumanosRESUMEN
AIM: To investigate the effectiveness of local halofuginone application for spinal epidural fibrosis (EF) after lumbar laminectomy in rats. MATERIAL AND METHODS: Forty rats were equally divided into four groups (Groups I-IV; 10 rats in each group), and lumbar laminectomy was performed under general anesthesia. After laminectomy, Group I received saline (NaCl 0.9%) locally (control), Group II received spongostan, Group III received 0.5 mL of halofuginone-impregnated spongostan, and Group IV received 0.5 mL of halofuginone. Spongostan was used to prolong the exposure period of halofuginone. All rats were sacrificed after four weeks and evaluated according to histopathological criteria. A p-value of < 0.05 was considered statistically significant. RESULTS: Fibrosis was significantly lower in Group IV than in Group I (p < 0.05). There was no significant difference in fibrosis between Group II/III and Group I. It was observed that spongostan increased fibrosis. CONCLUSION: Halofuginone helps prevent EF after spinal surgery. However, further clinical and experimental studies are needed to assess its safety in humans.
Asunto(s)
Espacio Epidural , Fibrosis , Laminectomía , Piperidinas , Quinazolinonas , Animales , Fibrosis/tratamiento farmacológico , Ratas , Piperidinas/administración & dosificación , Laminectomía/efectos adversos , Quinazolinonas/administración & dosificación , Quinazolinonas/uso terapéutico , Espacio Epidural/patología , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Vértebras Lumbares/cirugía , Modelos Animales de Enfermedad , Ratas Sprague-DawleyRESUMEN
Epidural fibrosis (EF) is a chronic, progressive and severe disease. Histone deacetylase 6 (HDAC6) regulates biological signals and cell activities by deacetylating lysine residues and participates in TGF-ß-induced epithelial-mesenchymal transition (EMT). Nevertheless, the effect and mechanism of HDAC6 in EF remain unclear. To investigate the effect and mechanism of HDAC6 inhibition on repressing epidural fibrosis. HDAC6 expression and α-smooth muscle actin (α-SMA) in normal human tissue and human EF tissue were assessed by quantitative real-time PCR (qRT-PCR) and western blotting. Human fibroblasts were treated with TGF-ß ± HDAC6 inhibitors (Tubastatin) and fibrotic markers including collagen I, collagen III, α-SMA and fibronectin were assessed using western blotting. Then TGFß1 receptor (TGFß1-R), PI3K and Akt were analyzed using qRT-PCR and western blotting. Rats were undergone laminectomy± Tubastatin (intraperitoneally injection; daily for 7 days) and epidural scar extracellular matrix (ECM) expression was gauged using immunoblots. Increasing HDAC6 expression was associated with α-SMA enrichment. Tubastatin remarkably restrained TGF-ß-induced level of collagen and ECM deposition in human fibroblasts, and the discovery was accompanied by decreased PI3K and Akt phosphorylation. Moreover, Tubastatin also inhibited TGF-ß-mediated HIF-1α and VEGF expression. In the epidural fibrosis model, we found that Tubastatin weakened scar hyperplasia and collagen deposition, and effectively inhibited the process of epidural fibrosis. These results indicated that Tubastatin inhibited HDAC6 expression and decreased TGF-ß/ PI3K/ Akt pathway that promotes collagen and ECM deposition and VEGF release, leading reduction of myofibroblast activation. Hence, Tubastatin ameliorated epidural fibrosis development.
Asunto(s)
Fibroblastos , Fibrosis , Histona Desacetilasa 6 , Ácidos Hidroxámicos , Transducción de Señal , Animales , Humanos , Masculino , Ratas , Actinas/metabolismo , Espacio Epidural/patología , Espacio Epidural/efectos de los fármacos , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Histona Desacetilasa 6/metabolismo , Histona Desacetilasa 6/antagonistas & inhibidores , Ácidos Hidroxámicos/farmacología , Indoles/farmacología , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
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.
Asunto(s)
Espacio Epidural , Lipomatosis , Humanos , Espacio Epidural/patología , Imagen por Resonancia Magnética/métodos , Lipomatosis/patología , Huesos/patologíaRESUMEN
BACKGROUND: Laminectomy is a widely employed surgical procedure for the treatment of spinal stenosis, but it may lead to epidural fibrosis (EF) and failed back surgery syndrome. Cinnamaldehyde, a phenylpropanoid found in cinnamon, has demonstrated antioxidant and anti-inflammatory properties. In the present study, we hypothesized that topical application and systemic administration of cinnamaldehyde could be helpful in the prevention of EF in a rat laminectomy model. METHODS: The rats were randomly assigned to control, local, and systemic Tween-80 and local and systemic cinnamaldehyde experimental groups (n = 6, per group). In the control group, just laminectomy was performed. In local treatment groups, applications were done just after the laminectomy onto dura. In systemic treatment groups, intraperitoneal administrations were performed following skin suturing. The degree of epidural fibrosis was evaluated macroscopically and histopathologically 4 weeks later. RESULTS: Macroscopic assessment revealed decreased EF with both topical and systemic cinnamaldehyde application, whereas microscopic examination results were not significant. CONCLUSIONS: Our findings provide the first experimental evidence of cinnamaldehyde's potential protective effects against EF.
Asunto(s)
Acroleína/análogos & derivados , Laminectomía , Microscopía , Ratas , Animales , Administración Tópica , Fibrosis , Espacio Epidural/patologíaRESUMEN
Background and purpose:
Epidural fibrosis after all spinal surgeries is an important surgical issue. Various biological and non-biological materials have been tried to inhibit epidural fibrosis, which is deemed to be the most important cause of pain after spinal surgery. Olive oil, nigella sativa oil and soybean oil employed in oral nutrition in clinics involving liquid fatty acids, palmatic acid, linoleic acid, stearic acid and palmitoleic acid. The effectiveness of olive oil, nigella sativa oil and soybean oil on epidural fibrosis was researched on for the first time in laminectomy model.
. Methods:Fifty adult male Wistar albino rats weighing between 300 and 400 grams were used in the research. A total of 5 groups were formed: sham (Group I) (n = 10), no application was created; Group II (n = 10) 1 cc saline; Group III (n = 10) 1 cc olive oil; Group IV (n = 10) 1 cc nigella sativa oil; Group V (n = 10); 1 cc soybean oil was applied topically to the epidural region after laminectomy. The total spine of the rats was dissected, histopathological and immunochemical measurements were conducted. Neuro-histopathological results were scored semi-quantitatively in terms of vascular modification, neuron degeneration, gliosis and bleeding criteria.
. Results:The lowest level of fibrosis and connective tissue proliferation was observed in the group where nigella sativa oil was used after the operation, followed by the group treated with olive oil and lastly with the group given soybean oil.
. Conclusion:Nigella sativa oil and olive oil are very efficient for lowering the degree of epidural fibrosis and adhesions following laminectomy and can be employed as a simple, inexpensive and highly biocompatible material in clinical practice.
.Asunto(s)
Aceites de Plantas , Aceite de Soja , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Aceite de Oliva/farmacología , Aceite de Oliva/uso terapéutico , Aceites de Plantas/farmacología , Aceites de Plantas/uso terapéutico , Fibrosis , Laminectomía/efectos adversos , Espacio Epidural/patologíaRESUMEN
Objective: To review the clinical research progress of spinal epidural lipomatosis (SEL). Methods: The clinical studies on SEL at home and abroad in recent years were extensively reviewed, and the pathogenesis, clinical and imaging manifestations, and treatment status of SEL were summarized and analyzed. Results: SEL is a disease characterized by compression of the spinal cord and nerve roots due to abnormal accumulation of epidural adipose tissue in the spinal canal. Its prevalence and diagnosis rate are low and the pathogenesis is not fully understood. MRI is the most sensitive and specific diagnostic test for SEL. Surgical decompression and removal of excess adipose tissue are the only options for patients with acute SEL or those who have failed conservative management, and conservative management should be considered for other patients. Conclusion: SEL is a rare disease and related research still needs to be improved. In the future, high-quality, multi-center and large-sample studies will be of great significance for evaluating the choice of treatment methods and effectiveness of SEL patients.
Asunto(s)
Lipomatosis , Enfermedades de la Médula Espinal , Humanos , Descompresión Quirúrgica/métodos , Espacio Epidural/patología , Espacio Epidural/cirugía , Lipomatosis/diagnóstico , Lipomatosis/cirugía , Imagen por Resonancia Magnética , Enfermedades de la Médula Espinal/cirugíaRESUMEN
BACKGROUND CONTEXT: Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate epidural fibrosis by suppressing proliferation and activation of fibroblasts, inflammation, and angiogenesis, and inducing apoptosis. PURPOSE: We reviewed and tabulated pharmaceuticals with their respective signaling axes implicated in reducing epidural fibrosis. Additionally, we summarized current literature for the feasibility of novel biologics and microRNA to lessen epidural fibrosis. STUDY DESIGN/SETTING: Systematic Review. METHODS: According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, nonrelevant articles, and insufficient detail of drug mechanism. RESULTS: We obtained a total of 2,499 articles from PubMed and Embase databases. After screening the articles, 74 articles were finally selected for the systematic review and classified based on the functions of drugs and microRNAs which included inhibition of fibroblast proliferation and activation, pro-apoptosis, anti-inflammation, and antiangiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis. CONCLUSION: This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy. CLINICAL SIGNIFICANCE: We expect that our review would enable researchers and clinicians to better understand the mechanism of anti-fibrosis drugs for the clinical application of epidural fibrosis therapies.
Asunto(s)
Laminectomía , MicroARNs , Animales , Laminectomía/efectos adversos , Fibrosis , Apoptosis , Modelos Animales , Espacio Epidural/patologíaRESUMEN
INTRODUCTION: Except for methylprednisolone, there is no current low-cost and low-side-effect drug/barrier method to prevent epidural fibrosis after spine surgery. However, the use of methylprednisolone has led to substantial controversy because of its serious side effects on wound healing. This study aimed to evaluate the effects of enalapril and oxytocin on preventing the development of epidural fibrosis in a rat laminectomy model. MATERIALS: Under sedation anesthesia, T9, T10, and T11 laminectomy was performed on 24 Wistar Albino male rats. The animals were then separated into four groups; Sham group (only laminectomy was performed; n = 6), MP group (laminectomy was performed and 10 mg/kg/day methylprednisolone was administered intraperitoneally (ip) for 14 days; n = 6), ELP group (laminectomy was performed and 0.75 mg/kg/day enalapril was administered ip for 14 days; n = 6), OXT group (laminectomy was performed and 160 µg/kg/day oxytocin was administered ip for 14 days; n = 6). Four weeks after the laminectomy, all the rats were euthanised, and the spines were removed for histopathological, immunohistochemical, and biochemical examinations. RESULTS: Histopathological examinations revealed that the degree of epidural fibrosis (X2=14.316, p = 0.003), collagen density (X2=16.050, p = 0.001), and fibroblast density (X2=17.500, p = 0.001) was higher in the Sham group and lower in the MP, ELP, and OXT groups. Immunohistochemical examinations showed that collagen type 1 immunoreactivity was higher in the Sham group and lower in the MP, ELP, and OXT groups (F = 54.950, p < 0.001). The highest level of α-smooth muscle actin immunoreactivity was seen in the Sham and OXT groups, and the lowest was in the MP and ELP groups (F = 33.357, p < 0.001). Biochemical analysis revealed that tissue levels of TNF-α, TGF-ß, IL-6, CTGF, caspase-3, p-AMPK, pmTOR, and mTOR/pmTOR were higher in the Sham group and lower in MP, ELP, and OXT groups (p < 0.05). The GSH/GSSG levels were lower in the Sham group and higher in the other three groups (X2=21.600, p < 0.001). CONCLUSION: The study results showed that enalapril and oxytocin, which are known to have anti-inflammatory, antioxidant, anti-apoptotic, and autophagy-related regenerative properties, could reduce the development of epidural fibrosis after laminectomy in rats.
Asunto(s)
Laminectomía , Oxitocina , Ratas , Animales , Laminectomía/efectos adversos , Ratas Wistar , Oxitocina/farmacología , Espacio Epidural/patología , Fibrosis , Metilprednisolona/farmacologíaRESUMEN
OBJECTIVE: Failed Back Surgery Syndrome (FBSS) refers to a subset of patients who have new or persistent pain after spinal surgery for back or leg pain. Epidural fibrosis (EF) is a common cause of FBSS. Many agents aiming to prevent EF have been tested. However, hemostatic agents are readily available at hospitals, easy to reach and frequently used. For these reasons, oxidized regenerated cellulose, polysaccharide hemostat, hemostatic thrombin-gelatin matrix and chitosan linear polymer were evaluated for their effects on epidural fibrosis on rats after laminectomy. METHODS: 40 Sprague-Dawley rats were randomly divided into 5 equal groups including the control group where only the laminectomy was performed. The other 4 groups received hemostatic agents after laminectomy. The rats were euthanized 45 days later and were assessed by a blinded observer to grade the fibrosis level. RESULTS: The study revealed that oxidized regenerated cellulose, polysaccharide hemostat and hemostatic thrombin-gelatin matrix lowered the epidural fibrosis grade which was statistically significant (p < 0.001). Although chitosan linear polymer created fibrosis similar to the control group it was not proven to be statistically significant (p = 0.8999). However, when compared with other hemostatic agents it resulted in a higher fibrosis grade (p < 0.001). CONCLUSION: The results obtained from this experimental study revealed that Pahacel, Sealfoam and Surgiflo, were effective in reducing epidural fibrosis after laminectomy in rats.
Asunto(s)
Quitosano , Hemostáticos , Ratas , Animales , Trombina/uso terapéutico , Gelatina , Ratas Sprague-Dawley , Hemostáticos/uso terapéutico , Fibrosis , Laminectomía/efectos adversos , Laminectomía/métodos , Polisacáridos , Dolor , Espacio Epidural/patologíaRESUMEN
OBJECTIVE: To demonstrate the effect of medical ozone therapy on the development of epidural fibrosis. METHODS: A total of 25 Sprague-Dawley male rats were randomly divided into 3 groups: a control group (L3-L4 laminectomy only), a systemic ozone therapy (SOT) group (L3-L4 laminectomy only + intraperitoneal 15 mL [30 µg/mL] ozone), and a local ozone therapy (LOT) group (L3-L4 laminectomy only + subcutaneous 15 mL [30 µg/mL] ozone). Ozone therapy was administered 4 times on a 3-day interval during the wound-healing process, with the first dose immediately administered after surgery. The effects of ozone therapy on vascular endothelial growth factor, inflammation, and epidural fibrosis between groups were evaluated. RESULTS: Staining with vascular endothelial growth factor was significantly less in the group that received SOT compared with the control group (P = 0.021). When the groups were compared in terms of inflammation, it was found that inflammation was less common in the SOT and LOT groups compared with the control group (SOT vs. control: P = 0.004 and LOT vs. control: P = 0.024), whereas inflammation was found to be significantly less in the SOT group compared with the LOT group (P = 0.008). In the histopathologic evaluation of epidural fibrosis, there was no significant difference between the SOT and LOT groups but less epidural fibrosis was observed in both groups compared to the control group (LOT vs. control: P = 0.037; SOT vs. control: P = 0.018). CONCLUSIONS: Medical ozone therapy may be an alternative method that can be used effectively and safely in the prevention of epidural fibrosis after laminectomy.
Asunto(s)
Inflamación , Factor A de Crecimiento Endotelial Vascular , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Fibrosis , Inflamación/patología , Cicatrización de Heridas , Laminectomía/métodos , Espacio Epidural/patologíaRESUMEN
BACKGROUND: The aim of this study was to investigate the protective and therapeutic effects of bovine amniotic fluid (BAF) on the inhibition of epidural fibrosis (EF) after experimental laminectomy. METHODS: Forty female Sprague Dawley rats were used. The amniotic fluids were collected from each trimester of a pregnant cow. The rats were divided into 5 groups. Whereas no laminectomy was applied to the control group, animals in the sham group underwent laminectomy. Laminectomy was performed in the animals in other groups and the operation area was closed by dripping 1 mL of BAF collected in 3 trimesters of pregnancy. Animals were killed 28 days after the operation. RESULTS: Compared with control, VEGF gene expression levels were downregulated approximately 5-fold in BAF-2. Whereas IL-6 was upregulated approximately 8-fold in the sham, it was downregulated 5-fold and 3-fold in BAF-1 and BAF-2, respectively. There was downregulation in BAF-2 and BAF-3 in terms of CD105 gene expression levels. TGFß1 was upregulated approximately 2-fold in the sham group and downregulated in BAF-1 and BAF-2. Although histopathologic alterations including EF grade and fibroblast cell density were found to increase in the sham group, all BAF treatment decreased those of alterations. The highest CD105 immunoreactivity was detected in the sham group. All BAF treatment markedly aggravated fibrosis via decreasing CD105 immunoreactivity. In terms of grading parameters, almost the closest grades to the control were determined in the BAF-2. BAF collected in the second trimester is most effective in healing of scar tissue and preventing fibrosis via decreasing microvessel and fibroblast densities. CONCLUSIONS: The results indicate that BAF may be used as a potential protective agent to prevent EF.
Asunto(s)
Líquido Amniótico , Espacio Epidural , Ratas , Bovinos , Animales , Femenino , Ratas Sprague-Dawley , Líquido Amniótico/metabolismo , Espacio Epidural/patología , Fibrosis , Cicatriz/patologíaRESUMEN
Excessive proliferation and migration of fibroblasts in the lumbar laminectomy area can lead to epidural fibrosis, eventually resulting in failed back surgery syndrome. It has been reported that laminin α1, a significant biofunctional glycoprotein in the extracellular matrix, is involved in several fibrosisrelated diseases, such as pulmonary, liver and keloid fibrosis. However, the underlying mechanism of laminin α1 in epidural fibrosis remains unknown. The present study aimed to explore the effect and mechanism of laminin α1 in fibroblast proliferation, apoptosis and migration, and epidural fibrosis. Following the establishment of a laminectomy model, hematoxylin and eosin, Masson's trichrome and immunohistochemical staining were performed to determine the degree of epidural fibrosis, the number of fibroblasts, collagen content and the epidural expression levels of laminin α1, respectively. Furthermore, a stable small interfering RNA system was used to knock down the expression of laminin α1 in fibroblasts. The transfection efficiency was confirmed by reverse transcriptionquantitative PCR and immunofluorescence staining. Western blot analysis, scratch wound assay, EdU incorporation assay, flow cytometric analysis and Cell Counting Kit 8 assay were performed to assess the proliferation, apoptosis, migration and viability of fibroblasts, as well as the expression levels of the AKT/mechanistic target of rapamycin (mTOR) signalingrelated proteins. In vivo experiments revealed that laminin α1 was positively and timedependently associated with epidural fibrosis. In addition, laminin α1 knockdown attenuated cell proliferation, viability and migration, and promoted apoptosis. Furthermore, the results revealed that the activation of the AKT/mTOR signaling pathway was involved in the aforementioned processes. Overall, the current study illustrated the positive association between laminin α1 and epidural fibrosis, and also verified the effect of laminin α1 on fibroblast proliferation, apoptosis and migration. Furthermore, the results suggested that the AKT/mTOR signaling pathway may serve a significant role in regulating the behavior of laminin α1induced fibroblasts.
Asunto(s)
Espacio Epidural , Proteínas Proto-Oncogénicas c-akt , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fibrosis , Espacio Epidural/patología , Serina-Treonina Quinasas TOR/metabolismo , Fibroblastos/metabolismo , Proliferación Celular , Sirolimus/farmacologíaRESUMEN
AIM: To investigate the efficacy of locally applied batimastat after laminectomy in preventing postoperative epidural fibrosis. MATERIAL AND METHODS: Thirty-two Wistar albino male rats weighing 200?250 g were used. The rats were assigned to four different groups (I-Control group, II-sham group, III-Laminectomy+Batimastat group, and IV-Laminectomy+SpongostanTM group). The rats were euthanized 28 days after surgery before TNF-?, IL6, IL-1?, IL10, TGF-?1, and MMP9 gene expression levels of tissue in the surgical area were determined with qPCR. TNF-?, IL6, and IL10 protein levels were also measured in both tissue and plasma. In addition, the surgical area was evaluated by histopathological and immunohistochemical methods. RESULTS: TNF-?, IL6, and IL-1? gene expression levels were higher in the batimastat group than in the control group. Whereas IL10 gene expression levels increased about two-fold in the sham and SpongostanTM groups, in the batimastat group, it was similar to that in the control group. TGF-?1 gene expression was three-fold higher in the sham group but was similar to that in the control group in both batimastat and SpongostanTM groups. MMP9 gene expression levels significantly decreased only in the batimastat group. In addition, fibrosis score, fibroblast cell count, inflammatory cell count, and CD105 expression decreased in the batimastat group relative to the control. CONCLUSION: Molecular and pathological examination results suggested that batimastat is an effective agent in reducing the occurrence of epidural fibrosis after laminectomy.
Asunto(s)
Laminectomía , Inhibidores de la Metaloproteinasa de la Matriz , Animales , Ratas , Espacio Epidural/patología , Fibrosis , Interleucina-1/farmacología , Interleucina-10/farmacología , Interleucina-6 , Laminectomía/efectos adversos , Metaloproteinasa 9 de la Matriz , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Ratas WistarRESUMEN
It is inevitable that scar formation occurs between the spinal dura and surrounding tissues after laminectomy. While extensive epidural fibrosis, which results in limited nerve root activity and severe pain, is the main cause of postoperative failed-back surgery syndrome. Novel biomaterial loading effective drugs based on reasonable design are eagerly needed for the safe and effective prevention of epidural adhesions. We filtrated a suitable dose of pirfenidone (PFD) to load hyaluronic acid methacryloyl (HAMA) hydrogel in vitro. And then, we compare PFD-loaded HAMA hydrogel with only using PFD or HAMA hydrogels after laminectomy by in vivo studies in rats. We describe a safe and efficient anti-adhesive PFD-loaded HAMA hydrogel that prevents epidural fibrosis through the stable and sustained release of PFD. It was shown that the PFD-loaded HAMA hydrogel effectively inhibited cell penetration and suppressed collagen I/III expression. Thus, it effectively prevented the formation of adhesions through pharmacological and physical processes. The PFD-loaded HAMA hydrogel can effectively prevent adhesion formation in both pharmacological and physical barrier effects.
Asunto(s)
Ácido Hialurónico , Hidrogeles , Ratas , Animales , Ácido Hialurónico/farmacología , Laminectomía/efectos adversos , Espacio Epidural/patología , Adherencias Tisulares/prevención & control , FibrosisRESUMEN
BACKGROUND: Though both neurosurgeons and orthopedic spinal surgeons are keenly aware of the clinical importance of epidural fat (EF), surgical practice varies amongst individual surgeons and across both fields. Thus, an in-depth understanding of the anatomical structure and composition of EF is vital, as it will play a significant role in the therapeutic management and the surgical choice of treatment. OBJECTIVE: We aim to extensively review the anatomical and biological properties of EF and further outline the surgical importance of EF management. STUDY METHODOLOGY: (i) MEDLINE search 1966-July 2019. Keywords: Review of the Literature. Authorship, Meta-analysis, Descriptive/Narrative overview; (ii) CINAHL search from 1982 to May 2019. Keywords: Review of the Literature spinal epidural fat; Authorship; Meta-analysis; Descriptive/Narrative overview; (iii) Hand searches of the references of retrieved literature; (iv) Personal and college libraries were searched for texts on research methods and literature reviews; and (v) 200 articles were downloaded, 50 were excluded because of similarity of topics and also because of new update on the same topics. (vi) Discussions with experts in the field of reviews of the literature. DISCUSSION: Though excessive or reductive amounts of EF usually exacerbates neurological symptoms and lead to various pathologic conditions such as spinal epidural lipomatosis, but there is no basic science, experimental, or clinical research that proves the role of EF in the aforementioned pathologic situations. CONCLUSION: Anatomical illustration, biological function and properties of EF knowledge may lead to changes in the stages of the surgical approach to avoid postoperative complications. However, the role of EF is exclusively bound to a scientific hypothesis as one cannot be sure if an excessive or reductive amount in EF is entirely responsible for the pathologic findings, or just only an incidental finding.
Asunto(s)
Espacio Epidural , Lipomatosis , Humanos , Espacio Epidural/cirugía , Espacio Epidural/patología , Complicaciones PosoperatoriasRESUMEN
We report the case of a rare lipoma arising in the epidural space of a 14-year-old boy without spinal dysraphism. Lipomas are rare in pediatric soft tissue tumors, accounting for only about 4% of cases. The incidence of an intraspinal epidural lipoma without spinal dysraphism is extremely rare in pediatric patients. In this case, the patient had progressive motor deficits in the lower extremities and difficulty in urination and defecation. Magnetic resonance imaging showed an extradural tumor compressing the spinal cord at the T3-T7 level. Because of the progressive neurological deficits, we performed an emergency surgery. The tumor was completely resected en bloc, and histopathology revealed mature adipose tissue with fibrous septa, diagnosed as atypical lipomatous tumor / well-differentiated liposarcoma. The patient fully recovered and there was no tumor recurrence for 6 years since the surgery. However, re-examination using fluorescence in situ hybridization after 6 years of surgery changed the diagnosis to lipoma as no amplification of murine double-minute type 2 oncogene was observed. In liposarcoma, histopathological diagnosis using fluorescence in situ hybridization is mandatory. Our case illustrates that immunohistochemical diagnosis alone can be misleading. Hence, prompt surgery is required for progressive neuropathy.
Asunto(s)
Lipoma , Liposarcoma , Disrafia Espinal , Adolescente , Animales , Niño , Espacio Epidural/patología , Humanos , Hibridación Fluorescente in Situ , Lipoma/complicaciones , Lipoma/diagnóstico , Lipoma/cirugía , Liposarcoma/diagnóstico , Liposarcoma/patología , Masculino , Ratones , Recurrencia Local de Neoplasia , ParaplejíaRESUMEN
Ewing sarcoma (ES) is a rare primary neoplasm in the lumbar adult spine and may mimic a benign tumor. In this case, after a patient's three-month history of lower back pain and rapidly progressing leg numbness and weakness, magnetic resonance imaging (MRI) showed a mass in the third lumbar vertebra. At a two-month follow-up, imaging showed a fracture, compression and lesion enlargement. Decompression and fixation confirmed ES, and the patient began combined radiotherapy and chemotherapy. Two months postoperatively, residual ES was suspected on MRI. The patient underwent a second surgery, and histopathology confirmed necrosis. A six-month follow-up after the first surgery showed no tumor recurrence. This case supports the inclusion of ES in the differential diagnosis of pathologic spinal fracture. Early decompression and spinal fixation are critical for preserving neurologic and spinal functions in ES complicated by a compression fracture. Combined adjuvant radiotherapy and chemotherapy remain the standard therapeutic strategy.