Topical administration of tranexamic acid for prevention of postoperative epidural fibrosis: insights from a rabbit laminectomy model

Abstract

Significant advancements in imaging and surgical methodologies have led to more frequent performance of neurosurgical procedures such as laminectomy in both animal and human patients. Epidural fibrosis (EF) is defined as the excessive formation of scar tissue in the epidural space after lumbar laminectomy, often resulting in recurring postoperative pain. Given the association between postoperative hematoma accumulation at the laminectomy site and the development of EF, the present study aimed to evaluate the preventive impact of tranexamic acid (TXA), an antifibrinolytic agent with well-recognized hemostatic properties across various surgical fields. A rabbit laminectomy model was constructed to assess its effectiveness in reducing EF formation. A total number of 18 adult New Zealand White male rabbits were randomly divided into two groups: The control (saline) group and the treatment (topical TXA) group. Each rabbit underwent a two-level laminectomy at L3-L4. The treatment group received 5.00 mL of 100 mg mL^-1 TXA solution applied topically to the laminectomy site, while the control group received 5.00 mL of saline. Postoperative evaluations included magnetic resonance imaging at week six to assess EF, followed by histopathological examinations to evaluate fibroblast cell density in scar tissue, EF grading and thickness of the dura mater. The analysis of magnetic resonance imaging and histopathologic data revealed significant differences between the two groups indicating that topical administration of TXA might be a promising approach for preventing EF.

Keywords: Epidural fibrosis; Laminectomy; Magnetic resonance imaging; Rabbit; Tranexamic acid.

Fig. 1

Intraoperative images of the rabbit laminectomy procedure. A) Paraspinal muscles are separated and retracted from the spinous processes (white arrows) of L3 and L4, with the processes being removed by a rongeur. B) The laminectomy site at the L3-L4 level after excision of the laminae and ligamentum flavum, revealing the exposed spinal cord with intact dura (black arrow). The black asterisk indicates the facet joint and the blue arrow indicates the posterior median spinal vein.

Fig. 2

Magnetic resonance imaging (MRI) observation of epidural fibrosis in rabbits 6 weeks postoperatively. Five consecutive T1-w axial MRIs of two rabbits, centered on the L3 - L4 disc level (indicated by asterisks in both panels). Perpendicular orange dotted lines are drawn to indicate quarters according to the grading system proposed by Ross et al. and modified by Lubina et al.¹⁹ The upper panel (A) depicts a control group rabbit, showing a relatively greater amount of EF and adhesion (white arrow) to the dura mater in the dorsal quarters. In (A-1), a pseudomeningocele caused by scar tissue regression is observed. In (A-2, A-3), scar tissue and adhesion are visible in more than 75.00% of both dorsal quarters consistent with a grade 4 Ross score. In (A-4), scar tissue and adhesion are visible in 25.00-50.00% of both dorsal quarters, consistent with a grade 2 Ross score. In (A-5), despite the absence of epidural fibrosis in the left dorsal quarter, scar tissue is visible in more than 75.00% of the right dorsal quarter, consistent with a grade 4 Ross score. The bottom panel (B) illustrates a TXA group rabbit with relatively less EF and adhesion to the dura mater in the dorsal quarters. In (B-1), there is no adhesion despite scar tissue formation. In (B-2, B-5), minimal scar tissue adhesion to the dura mater is observed in the left dorsal quarter while the other quarter remained free of adhesion. In (B-3), a lacuna between the epidural scar tissue and the dura mater at the disc level shows a large amount of epidural scar tissue in both dorsal quarters.

Fig. 3

Photomicrographs of Hematoxylin and Eosin-stained sections of laminectomy sites at 6 weeks post-operatively. A) 40 × magnification image of a TXA-treated rabbit demonstrating scar tissue without adherence to the dura mater, compatible with grade 0 EF; B) 40 × magnification image of a TXA-treated rabbit demonstrating only thin fibrous bands and minimal adhesion between the epidural fibrotic scar and dura mater, compatible with grade 1 EF; C) × 40.00 magnification image of a TXA-treated rabbit demonstrating epidural scar tissue with less than 2/3 adherence with the dura mater, compatible with grade 2 EF; D) 40 × magnification image of a control group rabbit demonstrating dense scar tissue adhering to more than 2/3 of the underlying dura mater, compatible with grade 3 EF. The bottom panel shows high-resolution images (400 ×) of the dotted rectangles in each of the upper panel images demonstrating the fibroblast density. E, F) Grade 1, G) grade 2 and H) grade 3 fibroblast density. Arrow indicates the dura mater. SC: Spinal Cord; EF: Epidural Fibrosis.