Effects of pirfenidone on experimental head injury in rats

Abstract

Traumatic brain injury (TBI) continues to be a significant public healthcare concern. Neuroinflammation that occurs in the secondary phase of TBI leads to cognitive and physical dysfunction. A number of therapeutic modalities have been evaluated in an attempt to find a suitable treatment. The only drug approved for the treatment of idiopathic pulmonary fibrosis, pirfenidone, has been evaluated for its antifibrotic, anti-inflammatory, and anti-oxidant properties for various disorders, but this is the first study to examine its effects in an experimental TBI model. Twenty-four Wistar rats were randomly divided into three groups: control, trauma, and pirfenidone. The two latter groups underwent experimental diffuse cortical injury mimicking TBI. Neurological assessment was performed using the Garcia test, histological analysis was performed to examine neuroprotective and anti-inflammatory effects, and biochemical analyses of neuron-specific enolase (NSE), S-100B, caspase-3, and thiobarbituric acid reactive substances were performed. The pirfenidone group had a better Garcia test score (P=0.001), an increased anti-inflammatory effect (P<0.001), and an enhanced neuroprotective effect (P=0.007) along with decreased NSE, S100B, and TBARS levels compared to the trauma group. However, pirfenidone did not show a beneficial effect on caspase-3 levels. Pirfenidone may help decrease mortality and morbidity rates after TBI through its anti-inflammatory and antioxidant effects.