Impact of sorafenib on epidural fibrosis: An immunohistochemical study

Abstract

Aim: To determine if sorafenib, an antineoplastic agent, could prevent the development of spinal epidural fibrosis (EF).

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: CD105; Osteopontin; Sorafenib; Spinal epidural fibrosis; Vascular endothelial growth factor.

Figure 1

Fibrosis development mechanism and the stage at which sorafenib prevents fibrosis is indicated. VEGF: Vascular endothelial growth factor.

Figure 2

Histopathological tissue section stained by HE. A: Grade-3 fibrosis and inflammatory cells in Group I; B: Grade-3 fibrosis and fibrous tissue in Group I; C: Grade 1 fibrosis in Group II. Star: Neural tissues; black arrow: Dura; blue arrow: Fibrosis tissue.

Figure 3

Immunohistochemical tissue section stained with anti-CD105 antibody. A: Grade-3 fibrosis in Group I; B: Grade-1 fibrosis in Group II. blue arrow: Fibrosis.

Figure 4

Immunohistochemical tissue section stained with anti-osteopontin antibody. A: Grade-3 fibrosis in Group I; B: Grade-1 fibrosis in Group II. Star: Neural tissues; black arrow: Dura; blue arrow: Fibrosis tissue.