Evaluation of topical Dexmedetomidine administration in postlaminectomy epidural fibrosis rat model

Abstract

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.

Dexmedetomidine Protects against Airway Inflammation and Airway Remodeling in a Murine Model of Chronic Asthma through TLR4/NF-κB Signaling Pathway

“…In our in vivo experiment, the pathological changes in the asthmatic airway, including goblet cell hyperplasia, extracellular matrix deposition, and increased airway smooth muscle mass were mitigated by DEX treatment. The suppressive effect of DEX on fibrosis has been investigated in various tissues and organs [50][51][52]. For example, in an acute kidney injury model, pretreatment with DEX alleviated tubulointerstitial fibrosis and the expression of inflammatory markers via the inhibition of α2-adrenergic receptor and hence hindered the progress of chronic kidney disease [51].…”

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

“…Although some studies have suggested the histopathological features of the EF, subsequent studies have rarely reported a better definition of its function. Spine physicians rarely pay attention to EF, and it is mostly linked to epidural fibrosis formation after spinal surgery [17][18][19][20][21][22][23][24][25][26] and clinically uncharacterized back pain [24,27,28]. Recently, novel studies with different views on EF have focused on its regenerative or immunomodulatory function, especially with respect to MSCs derived from EF.…”

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

“…In addition, TGF-1β released from fibroblasts increases the formation of fibrosis by causing a positive feedback on the fibrotic process. [4,9] There are many studies in the literature using a wide range of agents and affecting these molecular steps. Each treatment method used in these studies shows its main effect by affecting different steps of fibrosis formation.…”

“…Among the studies regarding the inflammatory response phase, the effect of specific inhibition of inflammatory cytokines and the use of anti-inflammatory agents on epidural fibrosis have been frequently examined in the literature. For the inhibition of specific inflammatory cytokines, etanercept, a TNF-α blocker, [1] tamoxifen, a TGF-β blocker, [7] methyl palmitate, [18] and dexmedetomidine [4] have been extensively investigated. Also, there are studies using diclofenac sodium [20] and curcumin [21] as anti-inflammatory agents.…”

“…[1,2] Epidural fibrosis develops as a result of the exaggerated healing tissue in this area, causing adhesions in the dura mater and nerve roots, and is one of the most important causes of failed back surgery syndrome caused by recurrent pain after surgery. [3,4] Revision surgeries performed due to recurrent pain after surgery may cause complications such as epidural bleeding, nerve root damage and dural lacerations, and worsen the clinical outcome. Therefore, the number of studies investigating 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.…”