Antifibrotic Effect of Topical 2-Mercaptoethanesulfonate (Mesna) in a Rat Craniectomy Model

Objective: Epidural adhesions that develop after decompressive craniectomy may complicate subsequent procedures by increasing operative difficulty and the risk of tissue injury. Mechanical barrier materials are commonly used, yet they do not directly modulate the inflammatory and fibrotic processes responsible for scar formation. This study investigated whether topical 2-Mercaptoethanesulfonate (Mesna) could reduce postoperative epidural fibrosis and adhesion formation in a rat craniectomy model.

Methods: Twenty-one adult male Wistar rats were randomly assigned to three groups (n=7 each): Sham, Vehicle (saline-soaked gelatin sponge), and Mesna (Mesna-soaked gelatin sponge). In the survival groups, re-exploration was performed after 4 weeks. Macroscopic adhesions were graded intraoperatively using the Rydell classification. Histopathological fibrosis and chronic inflammation were evaluated using Hematoxylin–Eosin and Masson’s Trichrome staining. Nonparametric statistical tests were applied.

Results: The Mesna group showed significantly lower adhesion scores compared with the Vehicle group (median 1.0 vs 3.0, P=0.019). Fibrosis and chronic inflammation scores were also significantly reduced in the Mesna group across both staining methods (all P<0.05). Adhesion severity correlated positively with fibrosis and inflammatory scores.

Conclusion: Topical Mesna application was associated with significantly lower macroscopic adhesion severity, histopathological fibrosis, and chronic inflammation in this experimental craniectomy model. These findings suggest a potential antifibrotic effect supported by macroscopic and histopathological parameters; however, the underlying molecular mechanisms remain to be clarified. Further dose-response, safety, mechanistic, and translational studies are required before clinical application.