Nintedanib Attenuates Epidural Fibrosis after Laminectomy in Rats

Area of Science:

• Neurosurgery
• Pharmacology
• Pathology

Background:

• Epidural fibrosis (EF) is a significant cause of morbidity following laminectomy.
• EF involves fibroblast activation, extracellular matrix deposition, and scar formation.
• Current treatments for post-laminectomy EF are limited.

Purpose of the Study:

• To investigate the antifibrotic, anti-inflammatory, and anti-angiogenic effects of nintedanib (NIN) in a rat model of post-laminectomy EF.

Main Methods:

• A rat model of laminectomy was established at the L3 level.
• Nintedanib (50 mg/kg/day) was administered orally for 28 days post-laminectomy.
• Histopathological analysis (H&E, Masson's trichrome), immunohistochemistry (α-SMA), and gene expression (TNF-α, IL-1β, VEGF, PDGFR, TGF-β1) were performed.

Main Results:

• Laminectomy induced significant increases in dura mater thickness, fibroblast density, collagen deposition, and epidural adhesions.
• Nintedanib treatment markedly reduced these fibrotic changes and suppressed myofibroblast activation (α-SMA).
• Nintedanib significantly downregulated key inflammatory (TNF-α, IL-1β), angiogenic (VEGF, PDGF), and fibrogenic (TGF-β1) markers.

Conclusions:

• Nintedanib effectively mitigated post-laminectomy epidural fibrosis through combined antifibrotic, anti-inflammatory, and anti-angiogenic mechanisms.
• Nintedanib improved dural structure and reduced scar formation, showing potential for preventing postoperative epidural adhesions.
• Further research is warranted to explore the clinical relevance of nintedanib for managing epidural fibrosis.