Nintedanib Attenuates Epidural Fibrosis after Laminectomy in Rats
JOURNAL OF KOREAN NEUROSURGICAL SOCIETY, cilt.69, sa.4, ss.563-574, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 69 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.3340/jkns.2025.0245
- Dergi Adı: JOURNAL OF KOREAN NEUROSURGICAL SOCIETY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Sayfa Sayıları: ss.563-574
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Hatay Mustafa Kemal Üniversitesi Adresli: Evet
Özet
Objective : Epidural fibrosis (EF) is a major contributor to postoperative morbidity following laminectomy (LAM). 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-LAM EF. Methods : Twenty-one male Wistar albino rats were assigned to three groups : control, LAM, and LAM + NIN. The LAM procedure was performed at the L3 level. NIN administration, following LAM, 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. alpha-smooth muscle actin (alpha-SMA) expression was evaluated using immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. Gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), platelet-derived growth factor receptor (PDGFR), and transforming growth factor-beta 1 (TGF-beta 1) was quantified to characterize inflammatory, angiogenic, and fibrogenic responses. Statistical comparisons were conducted using one-way analysis of variance or Kruskal-Wallis tests with appropriate post hoc analyses. Results : The LAM group exhibited marked post-LAM changes, including increased dura mater thickness (8.20 +/- 0.23 vs. 3.93 +/- 0.08 & micro;m 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 & micro;m; p<0.0001 vs. LAM), fibroblast density (p<0.01), and adhesion grade (grade 1, p=0.0012). alpha-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-alpha (p<0.001) and IL-1 beta (p<0.001), as well as angiogenic markers VEGF (p<0.001) and PDGFR (p<0.001), and fibrogenic mediators TGF-beta 1 (p<0.001) and alpha-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 LAM 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.