Akademik Veri Yönetim Sistemi
JOURNAL OF KOREAN NEUROSURGICAL SOCIETY, cilt.1, sa.1, ss.1-6, 2026 (SCI-Expanded, Scopus)
Objective
: Epidural fibrosis (EF) is a major contributor to postoperative morbidity following laminectomy. This study investigated the antifibrotic, anti-inflammatory, and anti-angiogenic effects of nintedanib (NIN), a multi-tyrosine kinase inhibitor, in a rat model of post-laminectomy EF.
Methods
: Twenty-one male Wistar albino rats were assigned to three groups: Control, Laminectomy (LAM), and Laminectomy + Nintedanib (NIN). The laminectomy procedure was performed at the L3 level. NIN administration, following laminectomy, was administered orally at a dose of 50 mg/kg/day for 28 days. Histopathological evaluations included hematoxylin-eosin staining for dura mater thickness and fibroblast density, and Masson’s trichrome staining for collagen deposition and adhesion grading. α-smooth muscle actin (α-SMA) expression was evaluated using immunohistochemistry and RT-qPCR. Gene expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor (PDGFR), and transforming growth factor-β1 (TGF-β1) was quantified to characterize inflammatory, angiogenic, and fibrogenic responses. Statistical comparisons were conducted using one-way ANOVA or Kruskal–Wallis tests with appropriate post hoc analyses.
Results
: The LAM group exhibited marked post-laminectomy changes, including increased dura mater thickness (8.20 ± 0.23 µm vs. 3.93 ± 0.08 µm in controls, p < 0.0001), elevated fibroblast density (p = 0.0006), severe collagen deposition, and high-grade epidural adhesions (Grade 3, p = 0.0006). NIN treatment attenuated these alterations, reducing dura mater thickness (4.80 ± 0.20 µm, p < 0.0001 vs. LAM), fibroblast density (p < 0.01), and adhesion grade (Grade 1, p = 0.0012). α-SMA immunoreactivity was high in LAM (Grade 3, p < 0.0001), whereas NIN significantly suppressed myofibroblast activation (Grade 1, p = 0.0012). NIN also significantly downregulated inflammatory mediators TNF-α (p < 0.001) and IL-1β (p < 0.001), as well as angiogenic markers VEGF (p < 0.001) and PDGF (p < 0.001), and fibrogenic mediators TGF-β1 (p < 0.001) and α-SMA (p < 0.01). These findings indicate that NIN suppresses fibroblast activation, extracellular matrix accumulation, and myofibroblast differentiation, thereby limiting epidural adhesion and scar maturation.
Conclusion
: Nintedanib effectively mitigated epidural fibrosis after laminectomy through combined antifibrotic, anti-inflammatory, and anti-angiogenic actions. By improving the dural structure and reducing key molecules that contribute to scar formation, NIN shows significant promise as a treatment to prevent postoperative epidural adhesions. Future studies with extended follow-up may help clarify its clinical relevance.