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Masson’s trichrome staining for epidural adhesion in the laminectomy sites treated with Sal B (a), Vehicle (b) or nothing (c). a: Loose scar tissues without adherence to the dura mater were seen in the Sal B group. b, c: Dense scar tissues adhered to the dura mater were observed in the Vehicle and Sham groups. The magnification was 100×. SC = spinal cord, D = dura mater, EF = epidural fibrosis, L = laminectomy.
Source publication
Epidural fibrosis (EF) is a common complication after laminectomy. Salvianolic acid B (Sal B) is a major bioactive component of a traditional Chinese medical agent, Salvia miltiorrhiza, which has shown anti-inflammatory, anti-fibrotic and anti-proliferative properties. The object of this study was to investigate the effect of Sal B on the preventio...
Contexts in source publication
Context 1
... the Sal B group, loose or little epidural scar adhesion was seen (Figure 2a). In the Vehicle group and the Sham group, dense epidural scar tissue with widespread adhe- sions to the dura mater was observed (Figure 2b,c). ...
Context 2
... the Sal B group, loose or little epidural scar adhesion was seen (Figure 2a). In the Vehicle group and the Sham group, dense epidural scar tissue with widespread adhe- sions to the dura mater was observed (Figure 2b,c). The immunohistochemistry analysis for VEGF showed that less VEGF was observable in the Sal B group versus the Vehicle and Sham groups. ...
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Background
Salvianolic acid B (Sal B) was newly reported to be able to attenuate fibrosis in the animal model. The aim of the present study was to investigate the effect of the intragastric application of Sal B on the prevention of epidural fibrosis (EF). Methods
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Citations
... The latest research has declared that constituents with anti-inflammatory (Wei et al. 2017), anti-proliferative (Chen et al. 2014), and anti-oxidant (Kuşaslan et al. 2020) activities can play a crucial role in preventing postoperative adhesion. PIPthe major bioactive component from Piper nigrum and Piper longumis an alkaloid with anti-inflammatory and antioxidant properties due to its ability to downregulate IL-6 and TNF-a inflammatory mediators and to inhibit oxidation reactions resulting from free radicals activity (Quijia et al. 2021); hence, represents a theoretical potential for postoperative adhesion prevention. ...
This study aimed to prepare piperine (PIP) loaded liposomes in hyaluronic acid (HA) hydrogel to provide a hybrid superstructure for postoperative adhesion prevention. Liposomes were prepared using thin-film hydration method. The optimised formulation was characterised by size, SEM, TEM, FTIR, encapsulation efficiency (EE)% (w/w), and release pattern. Liposome-in-hydrogel formulation was investigated by rheology, SEM, and release studies. The efficacy was evaluated in a rat peritoneal abrasion model. EE% (w/w) increased with increasing lipid concentration from 10 to 30; however, a higher percentage of Chol reduced EE% (w/w). The optimised liposome (EE: 68.10 ± 4.18% (w/w), average diameter: 513 ± 14.67 nm, PDI: 0.15 ± 0.04) was used for hydrogel embedding. No sign of adhesion in 5/8 rats and no collagen deposition confirmed the in vivo effectiveness of the optimised formulation. Overall, providing a sustained delivery of PIP, the developed liposome-in-hydrogel formulation can be a promising carrier to prevent postoperative adhesion.
... In addition to decreasing TGF-β expression, many factors may be effective in the emergence of this antifibrotic effect of pirfenidone. When analyzed in previous studies related to EF, it was revealed that reducing the effect of factors such as interleukin (IL)-1,IL-6, tumor necrosis factor (TNF)-α, platelet-derived growth factor (PDGF), FGF and vascular endothelial growth factor (VEGF) reduced EF formation (11,(22)(23)(24). When the studies related with pirfenidone were examined, a study conducted by Oku et al. revealed that pirfenidone decreased lung fibrosis by reducing the interferon (IF)-γ, bFGF and TGF-β expression (14). ...
Objective: To investigate the oral administration of pirfenidone on eperidural fibrosis formation.
Materials and Methods: Twenty-four rats were divided into three equal groups with eight rats in each group: group 1 (control), group 2 (25 mg/kg orally pirfenidone), and group 3 (50 mg/kg orally pirfenidone), and T11 and T12 laminectomies were performed in all rats, and then pirfenidone was given orally once a day for 30 days. At the end of the procedure, vertebral column samples were removed surgically. Epidural fibrosis grading, number of fibroblasts and arachnoidal involvoment were evaluated histopathologically. Gene expression of TGF-β1 and bFGF were analyzed using QRT-PCR, and synthesized proteins were examined using Western blot. Results: Pirfenidone doses of 50 mg/kg statistically significantly decreased EF formation compared with the controls and 25 mg/kg doses. The factors that play a role in the emergence of antifibrotic activity at 50 mg/kg doses were investigated, and it was revealed that pirfenidone reduced fibroblast proliferation, and showed this effect by reducing TGF-β1 and bFGF expression in fibrotic tissue.
Conclusion: Pirfenidone 50 mg/kg was shown to reduce fibroblast proliferation and suppress TGF-β1 and bFGF gene and protein expression.
... Laminectomy is commonly used in the treatment of lumbar disc herniation and its associated conditions (1). However, up to 40% of patients suffer from failed back surgery syndrome (FBSS), which is characterized by recurrent and continuous pain following neurosurgical interventions, such as lumbar laminectomy (2)(3)(4)(5). Extensive epidural fibrosis (EF), or scarring adjacent to the dura mater, may develop following lumbar laminectomy and may lead to clinically significant FBSS by compressing and irritating the surrounding anatomical structures (6)(7)(8). EF accounts for 24% of revision surgeries (9). ...
Epidural fibrosis (EF)‑induced failed back surgery syndrome (FBSS) in patients post‑laminectomy remains a medical challenge. Although the scarring mechanisms remain unclear, the majority of aetiological studies have reported fibroblast dysfunction. Honokiol, the major bioactive constituent of the magnolia tree, exerts a variety of pharmacological effects, including anti‑proliferative and anti‑fibrotic effects, on various cell types. The present study investigated whether honokiol attenuates EF progression. In vitro, it was found that honokiol inhibited excessive fibroblast proliferation induced by transforming growth factor‑β1 (TGF‑β1) and the synthesis of extracellular matrix (ECM) components, including fibronectin and type I collagen, in a dose‑dependent manner. These effects were attributed to the ability of honokiol to suppress the activity of connective tissue growth factor (CTGF), which is indispensable for the progression of fibrosis. Mechanistically, honokiol attenuated the TGF‑β1‑induced activation of the Smad2/3 and mitogen‑activated protein kinase (MAPK) signalling pathways in fibroblasts. In vivo, honokiol reduced the proliferation of fibroblasts and the synthesis of ECM components, thus ameliorating EF in a rat model post‑laminectomy. Taken together, these preclinical findings suggest that honokiol deserves further consideration as a candidate therapeutic agent for EF.
... 1,2 In some cases, recovery is achieved by light scale medical intervention or minimally invasive methods, but in some cases postoperative back pain is not relieved, even with interventions such as complex surgeries. 1,[3][4][5] Failed back surgery syndrome is characterized by recurrent continued pain after neurosurgical intervention such as lumbar laminectomy, and has gained the attention from spinal surgeons. [5][6][7] Epidural fibrosis is a natural outcome of laminectomy, being the formation of excessive scar tissue at the surgical site. ...
... 1,[3][4][5] Failed back surgery syndrome is characterized by recurrent continued pain after neurosurgical intervention such as lumbar laminectomy, and has gained the attention from spinal surgeons. [5][6][7] Epidural fibrosis is a natural outcome of laminectomy, being the formation of excessive scar tissue at the surgical site. 2,4,8 The literature has already reported that scars may cause clinically significant sequalae by creating adherences in between the tissues, or as a result of the dense fibrous tissue exerting pressure on the surrounding anatomical structures. ...
... 2,4,8 The literature has already reported that scars may cause clinically significant sequalae by creating adherences in between the tissues, or as a result of the dense fibrous tissue exerting pressure on the surrounding anatomical structures. [1][2][3][4][5][6][7][8][9] Although there is no consensus on the PRP was prepared by obtaining 10 cc blood from a rat in the donation group and put into tubes with citrate phosphonate dextrose (CPD). Additional 0.5 cc blood put into pediatric tubes with EDTA and sent to the autoanalyzer for cell count;10 cc blood with citrate were transported to the hematology laboratory in the cold chain for the preparation of PRP. ...
Objective:
Epidural fibrosis is one of the main reasons for requiring repeated surgical intervention. Our objective was to compare the effect of Platelet Rich Plasma (PRP) on the development of epidural fibrosis with collagen dural matrix and free autogenous fat graft.
Methods:
Male rats were separated into 3 groups. Laminectomy was implemented on the rats and epidural fat pad was placed in the first group (n = 7); equal size of collagen dural matrix was applied in the second group (n = 7); a single dose of PRP was applied in the third group (n = 7).
Results:
Epidural fibrosis was more common in the group that collagen dural matrix was applied when compared the ones that PRP was applied. PRP group presented better values in preventing epidural fibrosis when compared to the fat pad group, however this difference was not statistically significant.
Conclusion:
PRP is a material that can be easily obtained from the very blood of patients and at an extremely low cost; the main clinical relevance of our study is that the PRP might be an efficient material for better clinical results after laminectomy surgery due to its tissue healing and epidural fibroris preventing potentials. Level of Evidence V, Animal research.
... It was reported that these semifluid materials were able to not only protect the dura mater but also "wrap around" nerve roots. Nevertheless, these materials had some drawbacks in clinical use including uneven distribution, short duration of action at the site, and vulnerability to drainage [22,23]. In addition, some anti-fibrosis drugs and low-dose radiation have been reported to lessen postoperative adhesion by inhibiting the proliferation and function of fibroblasts, which provides a new approach to prevent epidural adhesion [24]. ...
... Sustained release anti-adhesion drugs are crucial for epidural adhesion. Ideally, a sustained release anti-adhesion drug should have a high initial rate of delivery (to treat the fibrosis derived from initial surgical trauma and hematomas) and then have an effective concentration over a long time period (to inhibit fiber maturity and contractures) [22]. In this study, TET release from the TET-PDLLA film in vitro was fast during the first 48 h and reached a second peak at day 38; total delivery lasted for approximately 66 days. ...
To investigate the drug release and anti-adhesion effects of a TET (tetrandrine)-loaded PDLLA (poly-dl-lactide) film. Detection of TET release in vitro was carried out by high-performance liquid chromatography (HPLC) every 2 days following immersion of the tetrandrine-loaded PDLLA film in simulated body fluid until the TET content of the eluate could not be detected. For the in vivo test, TET-loaded PDLLA films were implanted into animal laminectomy models and positive and blank control groups were also set up. Postoperative serum tests, and macroscopic and histological analyses at 1, 4, 8, and 12 weeks, were used to assess the effects of the film. Statistical analyses were performed by one-way ANOVA. The drug release of the tetrandrine-loaded PDLLA film in vitro showed two phases with a second release peak. Ultimately, the duration of continuous delivery was up to 66 days and the cumulative delivery rate was up to 93.18%. Scores for the proliferation of epidural scars or adhesion of the dura mater in the test group were much lower than those for the two control groups. Histological analysis revealed the test group had fewer inflammatory cells and fibroblasts, as well as fewer extracellular collagen fibers, and a lower histology score than those of the two control groups at all time points. Tetrandrine-loaded PDLLA film is a novel controlled drug release and anti-adhesion material in vitro and in vivo.
... Given the anti-fibrotic effect, traditional Chinese drugs have achieved positive effects in preventing postoperative fibrosis, including salvianolic acid B, 66 angelica sinensis, 67 safflower yellow 68 and daidzein. 69 Nonsteroidal anti-inflammatory drug (NSAIDs), including ketoprofen, 70 aceclofenac, 71 indomethacin 72 and ibuprofen, 73 could also modify local inflammation response and prevent post-operative fibrosis. ...
Post‐operative skeletal fibrosis is considered one of the major complications causing dysfunction of the skeletal system and compromising the outcomes of clinical treatment. Limited success has been achieved using current therapies; more effective therapies to reduce post‐operative skeletal fibrosis are needed. Stem cells possess the ability to repair and regenerate damaged tissue. Numerous studies show that stem cells serve as a promising therapeutic approach for fibrotic diseases in tissues other than the skeletal system by inhibiting the inflammatory response and secreting favorable cytokines through activating specific signaling pathways, acting as so‐called medicinal signaling cells. In this review, current therapies are summarized for post‐operative skeletal fibrosis. Given that stem cells are used as a promising therapeutic approach for fibrotic diseases, little effort has been undertaken to use stem cells to prevent post‐operative skeletal fibrosis. This review aims at providing useful information for the potential application of stem cells in preventing post‐operative skeletal fibrosis in the near future. This article is protected by copyright. All rights reserved
... Although various methods have been developed to prevent postsurgical adhesion formation, no effective treatment exists. 5,7,14,32,40,44 Thus, postsurgical adhesion formation has emerged as one of the major problems in these surgical procedures. ...
... may inhibit postsurgical adhesion formation by reducing inflammation. 5,6,37 Silk fibroin from Bombyx mori silkworms has been used for a variety of biomedical purposes, including as surgical sutures, because of its excellent biological and mechanical properties, lack of cytotoxicity, and low host inflammatory reaction. 15,[22][23][24] Rockwood et al. demonstrated that silk fibroin has been successfully used in various material forms, including films, sponges, hydrogels, and microparticles. ...
OBJECTIVE
Adhesion formation is one of the most common complications following laminectomy. The efficiency of antiadhesive agents is required to prevent postsurgical adhesion. Therefore, the authors investigated the effects of silk solution against laminectomy-induced dural adhesion formation in a rat model.
METHODS
The authors prepared the silk solution from silkworms. Laminectomies were performed between L3 and L5 in all rats. MediShield was used as a control. The effects of silk solution against laminectomy-induced dural adhesion formation and inflammation were confirmed by histological examination and Western blot analysis.
RESULTS
Laminectomy-induced dural adhesion formation was drastically reduced in silk solution–treated rats (Grade 2) compared to vehicle-treated rats (Grade 3). Dural adhesion formation was significantly reduced in rats that received treatment with silk solution or MediShield, which is a known antiadhesion drug. In addition, combined treatment with silk solution and MediShield showed greater reductions in inflammation compared to the silk solution– or MediShield-treated rats (p > 0.05).
CONCLUSIONS
In this study, the authors demonstrated that silk solution effectively reduced postlaminectomy dural adhesion formation in rats. Although further studies on the long-term effects are necessary to validate these results, silk solution may potentially serve as an antiadhesion agent in neurological procedures.
... Salvianolic acid B (Sal B) is a major bioactive component of a well-known traditional Chinese medical agent. 11 Sal B is extracted from the Chinese herb Salvia miltiorrhiza and has been attracting increasing amounts of attention due to its welldocumented biological potency. 12 Recently, Sal B has been widely accepted in the treatment of various diseases on account of its anti-inflammatory, anti-oxidative, anti-proliferative, and anti-fibrotic properties. ...
This study aimed to investigate the protective effects of salvianolic acid B (SA-B) on acute lung injury (ALI) through decreasing the expressions of channel kinase's TRPM6 and TRPM7. Wistar Septic rat models were established by lipopolysaccharide (LPS), which were separated into the control, lipopolysaccharide (LPS), SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6 and si-TRPM7 groups. Arterial blood gas, protein content, total white blood cell (WBC) count and the percentage of polymorphonuclear neutrophils (PMN%) were measured. Levels of TNF-α and IL-6 levels in bronchoalveolar lavage fluid (BALF) were monitored. Lung coefficient, myeloperoxidase (MPO) and superoxide dismutase (SOD) activity were conducted by MPO and SOD kit. The mRNA expressions of TRPM6 and TRPM7 were detected by qRT-PCR. Compared with the control group, the PaO2 and PaO2 /FiO2 values exhibited decreases in other group, while the PaCO2 value, protein content, total WBC, PMN%, TNF-α, IL-6 levels and lung coefficient values all increased. MPO activity in lung tissue increased, while SOD activity decreased. TRPM6 and TRPM7 expressions increased significantly. Compared with the LPS group, the SA-B, SA-B + si-TRPM6, SA-B + si-TRPM7, si-TRPM6 and si-TRPM7 groups had increased PaO2 and the PaO2 /FiO2 , while decreased PaCO2, protein content, total WBC, PMN%, TNF-α, IL-6 levels, and lung coefficient. MPO activity in lung tissue decreased while SOD activity increased. Decreased mRNA expressions of TRPM6 and TRPM7 in the SA-B, SA-B + si-TRPM6, and SA-B + si-TRPM6 groups were observed. Through decreasing the expressions of the channel kinase TRPM6 and TRPM7, SA-B protects against ALI in septic rats. This article is protected by copyright. All rights reserved.
... Salvianolic acid B (Sal B) is one of the major watersoluble bioactive component of the traditional Chinese medical agent, Salvia miltiorrhiza, and has been implemented as a treatment for cardiovascular diseases [11,12]. In our previous study, we evaluated the intragastric application of Sal B on the prevention of EF in vivo [13]. Based on our results and the latest studies [13,14], it was revealed that Sal B is able to exert antifibrotic effect through inhibition of the transforming growth factor-β (TGF-β) signaling pathway. ...
... In our previous study, we evaluated the intragastric application of Sal B on the prevention of EF in vivo [13]. Based on our results and the latest studies [13,14], it was revealed that Sal B is able to exert antifibrotic effect through inhibition of the transforming growth factor-β (TGF-β) signaling pathway. At the same time, another studies looking into Sal B's antiinflammatory and anti-fibrotic effects in different rat models were also recently reported [15][16][17]. ...
... Sal B treatment groups: salvianolic acid B (10, 30, and 50 mg/kg diluted in saline) or vehicle (saline) was administered intragastrically [13,17]. Vehicle treatment group: The same volume of saline was given in the same way. ...
Background
Salvianolic acid B (Sal B) was newly reported to be able to attenuate fibrosis in the animal model. The aim of the present study was to investigate the effect of the intragastric application of Sal B on the prevention of epidural fibrosis (EF). Methods
Forty healthy adult male Wistar rats were divided into four treatment groups (n = 10 per group): (1) 10 mg/kg Sal B, (2) 30 mg/kg Sal B, (3) 50 mg/kg Sal B and (4) Saline (vehicle treatment, control group). All animals underwent a laminectomy at the lumbar 1–2 (L 1–2) level. After intragastric treatment, all rats were sacrificed at post-operative week 8. The extent of the epidural scar, the regeneration of the vasculature and the expression levels of vascular endothelial growth factor (VEGF) were analysed. ResultsThe animals’ recovery was uneventful during the experimental period. The extent of the epidural scar, the regeneration of the vasculature and the expression levels of VEGF suggested better outcomes in the Sal B-treated groups. Sal B exerted the ability to prevent the formation of an epidural scar and vascularization at the laminectomy sites. The effects of Sal B were dose-dependent, with the 50 mg/kg Sal B group showing the best outcomes compared with the other groups. Conclusions
Post-operative intragastric application of Sal B can prevent the formation of epidural scarring. Sal B exerted these effects in a dose-dependent manner, and 50 mg/kg dose was shown to be the best effect in the present study. The results of this study reveal that Sal B could be a potential therapy for EF and valuable for further research.
... As previously reported, one of the most important mechanisms during the healing process is vascularization, which is regulated by several growth factors and modulators [7,21]. VEGF is one of the widely accepted critical factors. ...
... VEGF is one of the widely accepted critical factors. VEGF is thought to lead to the proliferation of endothelial cells, which can promote vascularization after wound healing [21,22]. A previous study showed that neutralizing VEGF had the effect of reducing fibroblasts proliferation and decreasing blood vessel, while activating the VEGF gene had the opposite effect [23]. ...
Background
Intra-articular adhesion is one of the common complications of post knee surgery and injury. The formation of joint adhesion can lead to serious dysfunction. Rosuvastatin (ROS) is a new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, with multiple biological effects. In our study, the object was to evaluate the effectiveness of ROS in the prevention of post-operative knee adhesion in rats.
Material/Methods
Femoral condyle exposing surgery was performed on 45 healthy Sprague Dawley rats. Gelatin sponges soaked with 20 mg/kg of ROS, 10 mg/kg of ROS, or saline were used to cover the surgical site. The post-operative knee joints were fixed in a flexed position with micro Kirschner wires for four weeks. ROS effectiveness for treating intra-articular adhesion was determined with visual score evaluation, hydroxyproline content, histological analyses, immunohistochemistry, and inflammatory and vascular endothelial growth factors expression.
Results
The animals’ recovery was stable after surgery. The hydroxyproline content, visual score, and inflammatory vascular growth factors expression levels suggested that, compared with the control group, the ROS treatment groups showed better outcomes. ROS prevented joint adhesion formation, collagen deposition, and vascularization at the surgical site, and also inhibited inflammatory activity post-operatively. Compared with the 10 mg/kg ROS group, the 20 mg/kg ROS group showed significantly better outcomes.
Conclusions
The local application of ROS reduced intra-articular adhesion formation, collagen deposition, and vascularization at the surgical site, and inhibited inflammatory activity post-operatively. These results suggested optimal concentration of ROS to be 20 mg/kg.
