©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Impact of sorafenib on epidural fibrosis: An immunohistochemical study
Osman Tanriverdi, Uzay Erdogan, Omur Gunaldi, Department of Neurosurgery and Psychiatry, University of Health Sciences, Bakırky Prof. Dr. Mazhar Osman Training and Research Hospital for Neurology, İstanbul 34303, Turkey
Canan Tanik, Department of Pathology, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34303, Turkey
Ilhan Yilmaz, Department of Neurosurgery, University of Health Sciences, Şişli Hamidiye Etfal Training and Research Hospital, İstanbul 34303, Turkey
Huseyin Utku Adilay, Department of Neurosurgery, Medical Faculty, Balıkesir University, Balıkesir 31300, Turkey
Ayca Arslanhan, Institute of Neurological Science, Marmara University, İstanbul 34303, Turkey
Metehan Eseoglu, Department of Neurosurgery, Medical Faculty, Medipol University, İstanbul 34303, Turkey
Author contributions: Tanriverdi O contributed to the conception, design, supervision and writing; Erdogan U contributed to the literature review and data collection; Tanik C contributed to the design, data collection, analysis and processing; Yilmaz I contributed to the writing and literature review; Gunaldi O contributed to the critical review and supervision; Adilay HU contributed to the data collection and materials; Arslanhan A contributed to the materials and data collection; Eseoglu M contributed to the literature review, materials and data collection.
Institutional animal care and use committee statement: Marmara University Local Ethics Committee for Animal Studies.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Osman Tanriverdi, MD, Doctor, Department of Neurosurgery and Psychiatry, University of Health Sciences, Bakırköy Prof. Dr. Mazhar Osman Training and Research Hospital for Neurology, Tevfik sağlam cad, No. 1, İstanbul 34303, Turkey. firstname.lastname@example.org
Received: April 27, 2018
Peer-review started: April 27, 2018
First decision: June 15, 2018
Revised: June 23, 2018
Accepted: July 31, 2018
Article in press: August 1, 2018
Published online: September 6, 2018
To determine if sorafenib, an antineoplastic agent, could prevent the development of spinal epidural fibrosis (EF).
The 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.
The 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.
Local 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.
Core tip: This study addressed the prevention of spinal epidural fibrosis (EF) by sorafenib, an antineoplastic agent, though immunohistochemical analyses of EF as a consequence of laminectomy in rats. The study demonstrated for the first time that the fibrosis thickness, inflammatory cell density, arachnoid adherences, fibrosis scores, and vessel count were significantly lower in the treatment group. These findings indicate that locally administered sorafenib may help reduce spinal EF after laminectomy without any significant complications or side effects.