Published online Sep 6, 2018. doi: 10.12998/wjcc.v6.i9.249
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
Spinal epidural fibrosis (EF) is a natural consequence of surgical trauma arising after laminectomy. In this study, we asked whether sorafenib can prevent the development of EF post-laminectomy using an immunohistochemical approach to quantify EF with CD105 and osteopontin antibodies.
EF is one of most common causes of failed back surgery syndrome, which occurs after laminectomy. Numerous causes and mechanisms have been proposed to explain its development after laminectomy. As treatment approaches for EF are associated with high rates of complications and failed surgery, the main goal is the prevention of EF. Many methods and medicines have been tried in order to prevent the development of EF. Sorafenib is an antineoplastic medicine that has demonstrated preventive effects against fibrosis due to an antiangiogenic mechanism involving inhibition of vascular endothelial growth factor (VEGF).
The goal of this study was to assess VEGF inhibition for the postoperative treatment of fibrosis.
Wistar albino rats (n = 16) were divided into two groups: control (laminectomy only) and sorafenib treatment (laminectomy + topical sorafenib). The animals were euthanatized after six weeks, and EF tissue was examined for histopathological changes after immunohistochemical staining and an EF grade was assigned. SPSS 15.0 for Windows (IBM, Armonk, NY, United States) was used for statistical analysis. Statistical significance was accepted as P < 0.05.
By light microscopy, EF thickness, inflammatory cell density and arachnoid adherences were higher in the control group compared to sorafenib-treated animals. Immunohistochemical staining for CD105 to identify microvessels revealed that EF grade was lower in the treatment group based on vessel count. Staining for osteopontin did not show any statistically significant differences in the extent of EF between groups. Significant differences in fibrosis score, fibroblast density, inflammatory cell density and CD105 immunostaining were observed between the sorafenib and control groups (P < 0.001). All control animals (Group I) received fibrosis scores of grade 3, while scores for sorafenib-treated animals (Group II) did not exceed grade 1 (P < 0.001). Fibroblast density was graded the highest in 100% of Group 1 animals but remained at grade 1 in Group II. Scores for inflammatory cell density were lowest in Group II but highest in Group I, as were scores for microvessel density assessed by CD105 immunostaining (P < 0.001). There was no significant difference in microvessel density scores between groups after osteopontin staining (P = 0.355). By light microscope, it could be seen that EF thickness, inflammatory cell density and arachnoidal adhesions were greater in control animals compared to Group II.
In this study, we examined the efficacy of topical treatment with sorafenib for the prevention of EF in an animal laminectomy model and analyzed immunohistochemical methods for the assessment of microvessel density in fibrotic lesions compared to conventional measures of fibrosis staging. Our results demonstrated that topical sorafenib was effective in reducing EF after laminectomy, likely due to decreased neovascularization resulting from the antiangiogenic effect of sorafenib on VEGF activity. We further show that immunohistochemical assessment of microvessel density using anti-CD105 antibodies provided a new measure of fibrotic development that was compatible with conventional methods of fibrosis staging.
In our study, the local application of sorafenib after laminectomy prevents EF. CD105 is a suitable marker for fibrosis, whereas osteopontin was not found to be reliable. Sorafenib was not observed to have any toxic effects or systemic side effects on normal tissues. Therefore, this application could be tested in clinical trials.