Effect of Cerebrospinal Fluid on Fibroblasts Concerning Epidural Fibrosis: An In Vitro Study

Abstract One of the most common treatments for lumbar disc herniation and other lumbar disorders is lumbar laminectomy. There may be some unwanted and serious complications with this procedure such as the “failed back surgery syndrome (FBSS)”. Epidural fibrosis (EF), mainly due to fibroblast proliferation, emerges as the main cause of failed back surgery syndrome. According to the current literature and practice techniques, different agents are being used to prevent EF formation. To date there is no single agreed upon treatment method of EF. In this study, dilutional effect of CSF, together with low potassium levels, on primary skin fibroblast cultures was studied as a possible material for EF prevention. CSF at different concentrations (0-100%) were tested to see its effect on Skin fibroblast proliferation. A wound healing assay was also performed to see the effect of CSF on wound healing. The cell proliferation goes up from 24h to 72hr in all CSF percentages from 0-75% but the proliferation was inhibited at 100% CSF. The “wound” is closed successfully in all CSF percentages between 0-75. The 100% CSF fails to completely close the wound. Adverse effects of low concentrations of potassium levels and dilutional effect of CSF may be a promising solution in the prevention of EF. Further in vivo and in vitro experiments are required to characterize its use.

[1]  D. Hao,et al.  Suberoylanilide hydroxamic acid attenuates epidural fibrosis via inhibiting myofibroblast differentiation and increasing fibroblast apoptosis. , 2020, European review for medical and pharmacological sciences.

[2]  J. Liang,et al.  Mocetinostat suppresses epidural fibrosis following laminectomy by inhibiting myofibroblast activation and increasing apoptosis. , 2020, European review for medical and pharmacological sciences.

[3]  Hui Chen,et al.  Emodin promotes fibroblast apoptosis and prevents epidural fibrosis through PERK pathway in rats , 2019, Journal of Orthopaedic Surgery and Research.

[4]  Hui Chen,et al.  Apigenin inhibits fibroblast proliferation and reduces epidural fibrosis by regulating Wnt3a/β-catenin signaling pathway , 2019, Journal of Orthopaedic Surgery and Research.

[5]  Carolyn A. Harris,et al.  Cerebrospinal fluid circulation: What do we know and how do we know it? , 2018, Brain circulation.

[6]  M. Yaman,et al.  Histopathologic Analysis of Tamoxifen on Epidural Fibrosis. , 2018, World neurosurgery.

[7]  Hui Chen,et al.  Methotrexate prevents epidural fibrosis through endoplasmic reticulum stress signalling pathway , 2017, European journal of pharmacology.

[8]  Lin Yu,et al.  Efficacy of Poly(D,L-Lactic Acid-co-Glycolic acid)-Poly(Ethylene Glycol)-Poly(D,L-Lactic Acid-co-Glycolic Acid) Thermogel As a Barrier to Prevent Spinal Epidural Fibrosis in a Postlaminectomy Rat Model , 2014, Clinical spine surgery.

[9]  M. Zeitlinger,et al.  Understanding the Activity of Antibiotics in Cerebrospinal Fluid in vitro , 2016, Pharmacology.

[10]  S. R. Snodgrass,et al.  A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans , 2015, Experimental Neurology.

[11]  Yu Sun,et al.  Mitomycin C induces fibroblasts apoptosis and reduces epidural fibrosis by regulating miR-200b and its targeting of RhoE. , 2015, European journal of pharmacology.

[12]  S. Standring.  Gray's Anatomy: The Anatomical Basis of Clinical Practice , 2015 .

[13]  B. Gürer,et al.  Evaluation of topical application and systemic administration of rosuvastatin in preventing epidural fibrosis in rats. , 2015, The spine journal : official journal of the North American Spine Society.

[14]  A. Levchenko,et al.  Human cerebrospinal fluid regulates proliferation and migration of stem cells through insulin-like growth factor-1. , 2015, Stem cells and development.

[15]  Henrik Zetterberg,et al.  Human cerebrospinal fluid increases the excitability of pyramidal neurons in the in vitro brain slice , 2015, The Journal of physiology.

[16]  Jinmin Zhao,et al.  Immunomodulatory effectiveness of licofelone in preventing epidural fibrosis in post-laminectomy rat , 2015, European Journal of Orthopaedic Surgery & Traumatology.

[17]  Jinmin Zhao,et al.  An experimental novel study: hyperbaric oxygen treatment on reduction of epidural fibrosis via down-regulation of collagen deposition, IL-6, and TGF-β1 , 2015, European Journal of Orthopaedic Surgery & Traumatology.

[18]  H. Sharma,et al.  All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats , 2014, Neuropharmacology.

[19]  Xiaohong Kong,et al.  ERK2 small interfering RNAs prevent epidural fibrosis via the efficient inhibition of collagen expression and inflammation in laminectomy rats. , 2014, Biochemical and biophysical research communications.

[20]  M. Oktay,et al.  Use of decorin to prevent epidural fibrosis in a post-laminectomy rat model. , 2014, European journal of pharmacology.

[21]  M. Ozdemir,et al.  Investigation of Efficacy of Mitomycin-C, Sodium Hyaluronate and Human Amniotic Fluid in Preventing Epidural Fibrosis and Adhesion Using a Rat Laminectomy Model , 2013, Asian spine journal.

[22]  Yang-jun Li,et al.  Clinical assessment of a CMC/PEO gel to inhibit postoperative epidural adhesion formation after lumbar discectomy: a randomized, control study , 2013, Archives of orthopaedic and trauma surgery.

[23]  Yang-jun Li,et al.  Erratum to: Clinical assessment of a CMC/PEO gel to inhibit postoperative epidural adhesion formation after lumbar discectomy: a randomized, control study , 2013, Archives of Orthopaedic and Trauma Surgery.

[24]  M. Vasei,et al.  The effect of methylene blue on peridural fibrosis formation after laminectomy in rats: an experimental novel study. , 2011, The spine journal : official journal of the North American Spine Society.

[25]  J. Nabekura,et al.  Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals , 2009, The Journal of Neuroscience.

[26]  Patrick J. Maloney.  Handbook of Neurosurgery , 2008, The Yale Journal of Biology and Medicine.

[27]  P. Scott,et al.  Deep dermal fibroblasts contribute to hypertrophic scarring , 2008, Laboratory Investigation.

[28]  L. Memış,et al.  Role of antifibrotic cytokine interferon-gamma in the prevention of postlaminectomy peridural fibrosis in rats. , 2008, Neurosurgery.

[29]  D. Ohnmeiss,et al.  Failed Back Surgery Syndrome: Diagnostic Evaluation , 2006, The Journal of the American Academy of Orthopaedic Surgeons.

[30]  F. Martinez,et al.  Mechanisms of pulmonary fibrosis. , 2004, Annual review of medicine.

[31]  R. Goodkin,et al.  Unintended "incidental" durotomy during surgery of the lumbar spine: medicolegal implications. , 1995, Surgical neurology.

[32]  F. Grinnell,et al.  Depletion of intracellular potassium disrupts coated pits and reversibly inhibits cell polarization during fibroblast spreading , 1993, The Journal of cell biology.

[33]  R. Thisted,et al.  Complications and demographic characteristics of patients undergoing lumbar discectomy in community hospitals. , 1989, Neurosurgery.