Pirfenidone Confines Glial Scar and Improves Functional Recovery after Compression Spinal Cord Injury

Abstract

Objectives: To investigate the anti-fibrotic and anti-inflammatory outcomes of pirfenidone through the intraperitoneal route to improve neurological recovery by reducing glial scar in rats aneurysm clip compression model of spinal cord injury.

Methodology: Thirty male Sprague Dawley rats were randomly assigned into three groups. All rats in all groups went through compression spinal cord injury induction. Group A, was treated with a placebo, group B was treated with pirfenidone 200 mg/kg/day, and group C was treated with pirfenidone 500 mg/kg/day. The experimental duration of 14 and 28 days was used to subgroup each group into groups 1 & 2 respectively (n = 5 in each subgroup). In order to inflict compression spinal cord injury, a 70-gram aneurysm clip was applied for one minute to the T7 level. To evaluate motor activity in the hind limbs of each subject, BBB scoring was used on the last day of the experiment. To determine collagen content in the injury lesions, Masson’s trichrome staining was applied to longitudinal spinal cord sections, followed by immunohistochemical staining with an anti-GFAP antibody for evaluating reactive astrocytosis. ImageJ Fiji software was used to quantify collagen deposition and reactive astrocytes.

Results: Between groups and within groups, a statistically significant difference was found in BBB scores, collagen deposition, and reactive astrocytes. There was an obvious upsurge in BBB scores, a reduction in the collagen deposition inside the injury lesion and reactive astrocytes around the injury lesion of pirfenidone-treated groups compared to the non-pirfenidone-treated SCI group.

Conclusion: Pirfenidone reduces collagen in the central core and reactive astrocytosis in the outer core of the glial scar by reducing fibrosis and inflammation. By limiting collagen deposition in injury lesions and inhibiting astrocyte activation, pirfenidone supports functional neurological recovery after spinal cord injury. Both of these factors play a critical role in inhibiting axonal regeneration succeeding spinal cord injury.