Rat Laminectomy Research Articles

The Effect of Halofuginone Use on Epidural Fibrosis After Spinal Surgery: An Animal Experiment.

To investigate the effectiveness of local halofuginone application for spinal epidural fibrosis (EF) after lumbar laminectomy in rats. 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. 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. Halofuginone helps prevent EF after spinal surgery. However, further clinical and experimental studies are needed to assess its safety in humans.

Evaluation of the effectiveness of oxytocin and enalapril in the prevention of epidural fibrosis developed after laminectomy in rats

IntroductionExcept 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. MaterialsUnder 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. ResultsHistopathological 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-β, 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). ConclusionThe 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.

Protective and Therapeutic Effects of Bovine Amniotic Fluids Collected in Different Trimesters on the Epidural Fibrosis After Experimental Laminectomy in Rats

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. 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. 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. TGFβ1 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. The results indicate that BAF may be used as a potential protective agent to prevent EF.

Continuous release of mefloquine featured in electrospun fiber membranes alleviates epidural fibrosis and aids in sensory neurological function after lumbar laminectomy.

Recurrent low back pain after spinal surgeries, such as lumbar laminectomy, is a major complication of excessive epidural fibrosis. Although multiple preclinical and clinical methods have been aimed at ameliorating epidural fibrosis, their safety and efficacy remain largely unclear. Single implanted electrospun fibrous membranes provide physical barriers that can decrease tissue fibrosis after surgery; however, they also trigger local inflammation due to the implantation of a foreign body, thus subsequently attenuating their anti-fibrosis properties. Here, we designed a strategy that permits easy incorporation of mefloquine into polylactic acid membranes, and stable long-term mefloquine release, to potentially improve anti-fibrosis effects and relieve or prevent low back pain. The electrospun fibrous membranes grafted with mefloquine showed a well-controlled early temporary peak release, and secondary drug release occurred smoothly over several weeks. Histopathological and histomorphometric results indicated that the drug-loaded membranes had excellent anti-fibrosis effects after laminectomy in rats. Inflammation and neovascularization at the surgical site indicated that the mefloquine-grafted electrospun fibrous membranes provided sustained anti-inflammatory outcomes while effectively alleviating associated neuropathic pain hypersensitivity. In summary, our study indicated that polylactic acid-mefloquine grafted electrospun fibrous membranes may be a potential local agent to mitigate epidural fibrosis and support sensory neurological function after laminectomy, thereby potentially improving patients' postoperative outcomes.

The Comparative Effects of Dexamethasone, Nanocurcumin, and Coenzyme Q10 Against Lumbar Laminectomy-Induced Epidural Fibrosis in a Rat Model.

One of the major problems in neurosurgical procedures is fibrosis formation. Therefore, the prevention of fibrosis is an important issue in spinal cord injury that needs to be addressed. No approved therapy has yet been found, and epidural fibrosis (EF) is a huge treatment challenge. In this regard, new drugs that can effectively prevent EF are still being considered. Hence, this study aimed to investigate the effects of dexamethasone (DEX), nanocurcumin (Nano-CUR), and coenzyme Q10 (CoQ10) on the prevention of EF in a rat laminectomy model. Thirty-five Sprague-Dawley male rats were randomly divided into 5 groups: sham group, laminectomy group, laminectomy+DEX group, in which 0.5ml DEX (8mg/ml) was applied locally on the laminectomy area, laminectomy+Nano-CUR group, in which 100mg/kg Nano-CUR was administered intraperitoneally once a day for 7days, and laminectomy+CoQ10 group, in which 30mg/kg CoQ10 was administered once daily intraperitoneally for 7days. After 4weeks, the vertebral columns were removed from L1 and L3 and prepared for histopathological assays. The local administration of DEX could not improve the histological parameters, and EF was induced by laminectomy after 4weeks. On the other hand, Nano-CUR could ameliorate EF at the laminectomy site compared to the laminectomy group, but the difference was not statistically significant. CoQ10 significantly reduced EF (P < 0.05), collagen density (P < 0.01), and inflammation in the arachnoid layer (P < 0.01). Our findings showed that Nano-CUR and CoQ10 had the potential to be used for treatment of EF.

Effectiveness of different epidural coverage materials for preventing postoperative scar hyperplasia and dural adhesion in spine

Objective: To analyze the effects and mechanisms of three commonly used epidural coverings, gelatin sponge, bovine Achilles tendon extract collagen and polyester urethane fiber, in preventing epidural scar adhesions after laminectomy in rats. Methods: Forty-eight adult Wistar rats were excised from L2 to L5 lamina to establish laminectomy models, and were divided into four groups with random number table according to different covering materials (12 rats in each group): blank group (group A), gelatin sponge group (absorbable, group B), polyester urethane fiber group (non-absorbable, group C) and bovine Achilles tendon extract collagen group (absorbable, group D). At 4 and 12 weeks postoperatively, the spinal tissues of the operated area were taken for gross observation (Rydell scar adhesion rating criteria) and histological observation (Nussbaum criteria); and the expression of three scar proliferation-related cytokines, basic fibroblast growth factor (bFGF), growth transforming factor β1 (TGF-β1) and vascular endothelial growth factor (VEGF), were measured in the peridural tissues. The differences between the indices in each group were analyzed and compared. Results: All 48 rats survived, and gross and histological findings at 4 and 12 weeks showed no dural adhesions in the gelatin sponge and bovine Achilles tendon extract collagen groups, adhesions in the polyester urethane fiber group, and heavy adhesions and spinal cord compression in the blank control group. There were significant differences in the Rydell grade and Nussbaum histological score between the absorbable material group and the non-absorbable group (both P<0.05). Western protein blotting at 4 and 12 weeks confirmed that the expression levels of three cytokines, including bFGF, TGF-β1, and VEGF, were lower in the absorbable material group than those in the non-absorbable group (all P<0.01). Immunofluorescence tests at 12 weeks confirmed that the expression of bFGF, TGF-β1 and VEGF were all lower in the gelatin sponge group (9.81±0.81, 12.42±2.35, 8.63±1.76) and the bovine Achilles tendon extract collagen group (12.70±2.02, 8.23±1.03, 10.19±2.67) than those in the polyester urethane fiber group (33.94±2.03, 30.29±2.76, 25.79±1.21) (all P<0.01). Conclusions: Bovine achilles tendon extract collagen and gelatin sponge can effectively reduce the hyperplasia of scar and dural adhesions after spinal surgery.

The Matrix Metalloproteinase Inhibitor Batimastat Reduces Epidural Fibrosis After Laminectomy in Rats.

To investigate the efficacy of locally applied batimastat after laminectomy in preventing postoperative epidural fibrosis. 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. 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. Molecular and pathological examination results suggested that batimastat is an effective agent in reducing the occurrence of epidural fibrosis after laminectomy.

Spinal epidural fibrosis following hemostatic agent employment

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.

Stereological and histopathological evaluation of the effect of Thymoquinone on peridural fibrosis following laminectomy in rats

Background/aim This study’s aim was to investigate the effects of thymoquinone, which is the essential bioactive component of the volatile oil of Nigella sativa on the peridural fibrosis in rats following laminectomy. Materials and methodsTwenty female Wistar Albino rats were used in our study. The rats were randomly divided into 2 groups: Sham and Surgery + Thymoquinone. Both groups underwent laminectomy at L1 under general anesthesia. The Sham group was not subjected to any drug application. The 2nd group was treated with intraperitoneal 10-mg/kg thymoquinone once per day for a period of 28 days, following the same surgical procedure. All of the group specimens were sacrificed after 4 weeks, and the laminectomy area was examined in terms of new bone volume, capillary volume, and fibrosis volume using stereological approaches. Results Statistically significant differences were found between the Sham and Surgery + Thymoquinone groups in terms of new bone volume (P = 0.01), capillary volume (P = 0.01), and fibrosis volume (P < 0.001). It was noted that Thymoquinone caused a significant increase in new bone volume, vascular volume and, a significant decrease in fibrosis volume. ConclusionThe results of our study indicate that thymoquinone is effective in decreasing peridural fibrosis when applied to a laminectomy model.

LncRNA CASC9 attenuates lactate dehydrogenase-mediated oxidative stress and inflammation in spinal cord injury via sponging miR-383-5p.

Long non-coding RNAs (lncRNAs) play important roles in various diseases, but the effect of lncRNA CASC9 on spinal cord injury (SCI) remains unclear. Therefore, the present study was conducted to explore the role of this lncRNA in SCI. SCI model was established by laminectomy in rats in vivo or induced by LPS in PC12 cells in vitro. Methylprednisolone (MP) was used for treatment in vivo. Spinal cord tissues were stained with H&E, and the oxidative stress- and inflammation-related factors were detected using their commercial kits. Cell apoptosis was determined using flow cytometry assay. Relative expression of corresponding genes was measured using qRT-PCR and western blotting. Luciferase reporter assay was used to verify binding site between CASC9 and miR-383-5p, as well as miR-383-5p and LDHA. The results showed that lncRNA CASC9 was downregulated and miR-383-5p was upregulated in SCI rats and LPS-induced PC12 cells. Severe histological injury and increased water content were also found in SCI rats. Increased levels of LDH, MDA, lactic acid, TNF-α, and IL-1β were found in SCI rats and LPS-induced PC12 cells. These changes could be reversed by MP treatment in vivo or overexpression of CASC9 in vitro. Besides, overexpression of CASC9 decreased cell apoptosis and protein expression of LDHA and increased protein expression of Nrf2 and HO-1 in LPS-induced PC12 cells. Furthermore, miR-383-5p was a direct target of CASC9 and was negatively regulated by CASC9. LDHA was a direct target of miR-383-5p and was negatively regulated by CASC9. In conclusion, lncRNA CASC9 exerted a protective role against oxidative stress, inflammation, and cell apoptosis in SCI, providing a novel therapeutic target or prognostic factor for SCI.

Impact of radial extracorporeal shock wave therapy in post-laminectomy epidural fibrosis in a rat model.

Objectives This study aims to investigate the effect of radial extracorporeal shock wave therapy (rESWT) treatment in the prevention of epidural fibrosis after laminectomy in rats.Materials and methods Eighteen 16-month-old male Sprague-Dawley rats weighing 300 g were used in this experimental study between November 2019 and February 2020. The rats were randomly divided into two groups as the control group (L3-L4 total laminectomy without any treatment) and the study group (L3-L4 total laminectomy plus rESWT). The rats were sacrificed at the postoperative sixth week and the lumbar spine was excised en bloc, fixed, and decalcified. Sections were stained with hematoxylin-eosin to evaluate epidural fibrosis, acute inflammation, chronic inflammation, and vascular proliferation.Results The median value and standard deviations were obtained based on histological examinations. Accordingly, epidural fibrosis decreased significantly in the study group compared to the control group. There was no statistically significant difference between the groups in terms of acute and chronic inflammation response and vascular proliferation.Conclusion The rESWT application immediately after surgery is effective in preventing epidural fibrosis after laminectomy in rats.

Dehydrated human amnion/chorion membrane allograft for preventing epidural fibrosis after laminectomy: an experimental rat model

Objectives: Post-laminectomy syndrome due to epidural fibrosis (EF) is a common cause of persistent low back pain after lumbar spinal surgery and is challenging for both surgeons and patients. The current experimental study aimed to investigate the effect of dehydrated human amnion/chorion membrane (dHACM) allograft for preventing EF formation following lumbar laminectomy. Methods: Sixteen Sprague–Dawley rats equally divided into two groups underwent lumbar laminectomy. Group A, the control group, underwent lumbar laminectomy with standard closure. Group B, the experimental group, additionally received epidural dHACM allografts during the procedure. After 45 days of follow-up, the rats were sacrificed, and the harvested tissues were histopathologically evaluated for EF. Results: Compared with Group A, Group B showed significantly less EF generation (p &amp;lt; 0.001), implying that dHACM allografts effectively prevent EF. Conclusions: This study demonstrated that dHACM can effectively reduce EF formation after spinal laminectomy in rats.

Chitosan-Hydroxyapatite Scaffold for Tissue Engineering in Experimental Lumbar Laminectomy and Posterolateral Spinal Fusion in Wistar Rats.

Study DesignExperimental study with an animal model.PurposeTo evaluate the role of a chitosan and hydroxyapatite composite for spinal fusion in a lumbar experimental model based on regenerative tissue engineering principles.Overview of LiteratureChitosan and hydroxyapatite represent an alternative biodegradable implant material for tissue engineering and regeneration. The combination of chitosan and hydroxyapatite in a 20:80 ratio could potentiate their individual properties as an implantable composite for experimental laminectomy.MethodsPhase I: design and synthesis of a porous composite scaffold composed of chitosan-hydroxyapatite using a freeze drying technique. Phase II: experimental microsurgical lumbar laminectomy at L5. A total of 35 Wistar rats were categorized into three experimental groups: control (laminectomy alone), experimental (laminectomy with implant), and reference (intact spine) (n=5 per group). Postoperative structural and functional evaluations were performed using computed tomography scans. In addition, radiologic, clinical, histological, and immunohistochemical microstructures were evaluated.ResultsAt the laminectomy site, the composite implant induced bone regeneration, which was observed in the axial reconstruction of the rat lumbar spine in all cases. Biomechanical changes in the lumbar spine were observed by radiology in both groups after the surgery. The posterolateral space was covered by a bone structure in the treated spine, a condition not seen in the control group. The range of motion was 7.662°±0.81° in the scaffold group versus 20.72°±3.47° in the control group. Histological findings revealed qualitatively more bone tissue formation in the implant group.ConclusionsA composite of chitosan-hydroxyapatite at a 20:80 ratio induced bone formation after experimental laminectomy in rats and led to spinal fusion, which was assessed by radiology and biomechanical tests. No functional complications in posture or walking were observed at 90 days post-surgery, despite biomechanical changes in the spine.

Artesunate inhibits fibroblasts proliferation and reduces surgery-induced epidural fibrosis via the autophagy-mediated p53/p21waf1/cip1 pathway

Fibroblast proliferation is considered to be a major cause in the process of epidural fibrosis formation. Autophagy is a tightly-regulated catabolic process in charge of degrading intracellular components. Although autophagy has been associated with fibrosis of different tissues, the effect of autophagy on epidural fibrosis is still unknown. The aim of this study was to investigate the function and mechanism of autophagy induced by Artesunate (ART), a classical antimalarial agent extracted from the Chinese medicinal herb. In vitro, the effect of ART on inducing fibroblast autophagy was evaluated via LC3 immunofluorescent staining, Transmission Electron Microscopy (TEM) and western blotting analysis. Moreover, the effect of ART on inhibiting fibroblast proliferation was investigated by CCK-8 assay, EdU incorporation assay, flow cytometry and western blotting analysis. Results indicated that ART could induce autophagy and inhibit proliferation in fibroblasts. The inhibitory effect of ART on fibroblast proliferation was associated with the upregulation of p53 and p21waf1/cip1 proteins. Intriguingly, 3-MA, a classical autophagy inhibitor, attenuated ART-induced p53/p21waf1/cip1 pathway activation and fibroblast proliferation inhibition. In vivo, the effect of ART on reducing epidural fibrosis was detected by histological macroscopic assessment, hydroxyproline content analysis, histological and immunohistochemical staining. The results revealed that ART had significant suppressive effects on epidural fibrosis following laminectomy in rats. In conclusion, this research demonstrated that ART could inhibit fibroblast proliferation and reduce epidural fibrosis formation after laminectomy, and the potential mechanism might through autophagy cascade-mediated p53/p21waf1/cip1 pathway. It might provide a novel reagent for reducing epidural fibrosis after spinal laminectomy surgery.

Impact of sorafenib on epidural fibrosis: An immunohistochemical study.

AIMTo determine if sorafenib, an antineoplastic agent, could prevent the development of spinal epidural fibrosis (EF).METHODSThe study used CD105 and osteopontin antibodies in an immunohistochemical approach to quantify EF that occurred as a consequence of laminectomy in rats. Wistar albino rats (n = 16) were divided into two groups: control (L1-2 level laminectomy only) and sorafenib treatment (L1-2 level laminectomy + topical sorafenib). The animals were euthanatized after 6 wk, and the EF tissues were examined for histopathological changes after immunohistochemical staining. The EF grades were assigned to the tissues, and the treatment and control groups were compared.RESULTSThe EF thickness, inflammatory cell density, and arachnoid adherences determined by light microscopy were significantly higher in the control group compared to the sorafenib-treated group. Based on fibrosis scores, the extent of EF in the treatment group was significantly lower than in the controls. Immunohistochemical staining for CD105 to identify microvessels revealed that the EF grades based on vessel count were significantly lower in the treatment group. Staining for osteopontin did not show any significant differences between the groups in terms of the extent of EF. The staging of EF based on vascular counts observed after immunohistochemical staining for CD105, but not for osteopontin, was compatible with conventional staging methods. Neither toxic effects on tissues nor systemic side effects were observed with the use of sorafenib.CONCLUSIONLocal administration of sorafenib significantly reduced post-laminectomy EF. Decreased neovascularization in spinal tissue may be due to the sorafenib-induced inhibition of vascular endothelial growth factor.

Effect of Local N-acetyl-cysteine in the Prevention of Epidural Fibrosis in Rat Laminectomy Model.

Background:Epidural fibrosis is a major contributing factor to the onset of failed back syndrome. Many studies have attempted to prevent this physiological response. Interestingly, N-acetyl-cysteine (NAC) has been effective in some cases in the treatment of pulmonary fibrosis.Objective:The objective of this study was to determine whether local NAC is an effective way to prevent epidural fibrosis after laminectomy in rats.Materials and Methods:Twenty Wistar rats were used in this study. Animals were divided into two groups: NAC group and a control group. We performed two-level laminectomy (L4–L5) in these rats. Rats in the control group just had laminectomy, and in the other group, L4 and L5 laminectomy followed by local treatment with NAC. Four weeks later, the rats were killed, and the laminectomy level was subjected to histopathological examination to evaluate epidural fibrosis and fibroblast density.Results:Histopathological examination showed that after 4 weeks of surgery the NAC group had significantly less epidural fibrosis and fibroblasts compared with control group.Conclusion:Our findings indicate that NAC decreased spinal epidural fibrosis after laminectomy in rats.

Comparison of the Effects of Contractubex Gel and Benzothiazole After Topical Application in an Experimental Model of Epidural Fibrosis in Rats

Postoperative epidural adhesion is a frequent cause of failed back surgery syndrome, manifesting with back and leg pain or neurologic deficits. Development of preventive measures for epidural adhesion after laminectomy is critical to improve outcomes of lumbar surgery. We hypothesized that positive effects of topical application of Contractubex (CTX) gel and benzothiazole (BT) individually and in combination could aid in preventing epidural fibrosis in a rat laminectomy model. Rats were randomly assigned to 2 control and 5 experimental groups (n= 8 for each group). The control(-) group received no surgery, whereas the control(+) group underwent laminectomy without any drug administration. In experimental groups, study agents applied to dura mater after laminectomy were 100mgCTX, 2.5%BT, 5%BT; 100mgCTXplus2.5%BT, and 100mgCTXplus5%BT. Laminectomy was performed at the L3 level for all rats. The extent of epidural fibrosis was assessed 4 weeks later macroscopically and histopathologically. Hepatic and renal toxicity of study drugs was assessed histopathologically. Topical CTX and BT individually and in combination reduced epidural fibrosis after laminectomy in rats. Although a meaningful decrease of epidural fibrosis with individual application of CTX and BT (2.5% or 5%) was obtained (P < 0.05), the effect of their combination was more pronounced without meaningful hepatic and renal toxicity (P < 0.05). Combined use of topical CTX and BT could be a potential therapy for epidural fibrosis. Further research with this agents for the prevention of epidural fibrosis is warranted.

Evaluation of topical Dexmedetomidine administration in postlaminectomy epidural fibrosis rat model

Epidural fibrosis is a challenging topic in spinal surgery. Numerous clinical and experimental studies have been focused on this issue to clarify problems faced in spinal procedures for the patient as well as the surgeon and find out new methodologies. Dense cytokines and growth factors which are released from inflammatory cells have been suggested to play a major role in the inception and progression of fibrosis. One of the most investigated and important actor in epidural fibrosis is assumed to be the transforming growth factor-1β (TGF-1β) formation. Studies showed that Dexmedetomidine (DEX) downregulates TGF-β pathway with its anti-inflammatory and antioxidant effects. From this point of view, for the first time in the literature we try to observe if there will be an effect of topical DEX administration over epidural fibrosis in a rat model. We hypothesized that DEX might have preventive effects on epidural fibrosis via anti-inflammatory and antioxidant effects. Twenty-four adult male Wistar albino rats were randomly assigned to three groups (Topical DEX, Spongostan, Laminectomy). A total laminectomy was performed at the L3-L5 level and then the ligamentum flavum and epidural fat tissue were cleared away from the surgical site. Histopathological assessment was performed postoperatively after 4 weeks. Our study revealed that topical DEX administration may have effects on reducing epidural fibrosis. Topical DEX administration may be helpful in preventing epidural fibrosis after laminectomy in rats through multiple anti-inflammatory and antioxidant mechanisms as well as through TGF -1β pathway.

Histopathologic Analysis of Tamoxifen on Epidural Fibrosis.

Epidural fibrosis is a challenging topic in spinal surgery. This phenomenon constitutes one of the main reasons behind postlaminectomy syndrome or failed back surgery syndrome, which leads to persistent back and leg pain in association with compression and/or stretching the nerve root or the dura. The exact mechanism of action in epidural fibrosis is complex and remains uncertain. Excessive deposition of collagen, fibronectin, and dermatan sulfate, known as the "extracellular matrix," and decrease of tissue cellularity results in epidural fibrosis. The most investigated and important actor in epidural fibrosis as well as in other forms of aberrant wound healing is presumed to be transforming growth factor-1β formation. Tamoxifen (TAM), a synthetic nonsteroidal antiestrogen used in breast cancer, is also effective in inhibiting fibroblast proliferation via downregulation of transforming growth factor-1β. Twenty-four adult male rats were randomly divided into 3 groups. Laminectomy was the sole intervention in the control group. Spongostan was placed in the operation lodge after laminectomy in the second group. In the treatment group, TAM was administrated orally after laminectomy. Epidural fibrosis, dural thickness, inflammatory response, and arachnoidal involvement were evaluated and graded histopathologically. Epidural fibrosis, dural thickness, and inflammatory response in the subjects treated with TAM were significantly less than in the control and Spongostan group and the differences were statistically significant. Although arachnoidal involvement was observed in a subject in the TAM group, the differences between all groups weren't statistically significant. Tamoxifen reduced epidural fibrosis, dural thickness, and inflammatory response after laminectomy in rats.

Homoharringtonine prevents surgery-induced epidural fibrosis through endoplasmic reticulum stress signaling pathway

Surgery-induced epidural fibrosis after laminectomy often results in poor clinical outcomes. Fibroblasts proliferation is considered to be one of the major causes of epidural fibrosis formation. Previously, there was no research about the effect of Homoharringtonine(HHT) on inhibiting fibroblast proliferation and reducing epidural fibrosis. Here, we performed in vitro and in vivo experiments to explore the effect of HHT on inhibiting fibroblast proliferation, inducing fibroblast apoptosis and preventing epidural fibrosis formation. In vitro, the effect of HHT on inhibiting fibroblasts was detected by CCK-8 assay. Besides, the effect of HHT on causing fibroblast apoptosis was investigated via Western blots, flow cytometry and TUNEL assay. Results suggested that HHT could inhibit fibroblasts proliferation and induce apoptosis. And the marker proteins of endoplasmic reticulum (ER) stress were also changed positively. In vivo, histological macroscopic assessment, hydroxyproline content analysis and histological staining were used to detect the effect of HHT on reducing epidural fibrosis. The results showed that HHT had positive suppressive effects on epidural fibrosis following laminectomy in rats. TUNEL assay in epidural tissue suggested that HHT could obviously induce fibroblasts apoptosis. Immunohistochemistry staining showed that the expression of two important ER stress markers(78-kDa glucose-regulated protein and C/EBP homologous protein) were also increased. In conclusion, this research showed that HHT could reduce epidural fibrosis formation after laminectomy, and the potential mechanism might through inhibiting fibroblasts proliferation and inducing fibroblasts apoptosis via ER stress signaling pathway. It might provide a novel agent for reducing epidural fibrosis after laminectomy surgery.