Rosiglitazone exerts neuroprotective effects via the suppression of neuronal autophagy and apoptosis in the cortex following traumatic brain injury.

Abstract

Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity in adults and children worldwide. Recent studies have demonstrated that both apoptosis and autophagy participate in TBI-induced neuronal cell death and functional loss. The peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist rosiglitazone (RSG) is a well-known anti-inflammatory, which carries out its effects via the activation of PPAR-γ. Previous studies have suggested that RSG may exert neuroprotective effects in animal models of both chronic and acute brain injury; however, whether RSG is involved in autophagic neuronal death following TBI remains to be elucidated. The present study aimed to determine whether RSG carries out its neuroprotective properties via the attenuation of neuronal apoptosis and autophagy, following TBI in a rat model. Furthermore, the role of RSG was investigated with regards to the modulation of inflammation and glutamate excitotoxicity, and the impact of RSG on functional recovery following TBI was determined. The rats were subjected to controlled cortical impact injury, prior to being randomly divided into three groups: A sham-operated group, a TBI group, and an RSG treatment group. The RSG treatment group was intraperitoneally treated with 2 mg/kg RSG immediately after TBI. The results of the present study demonstrated that RSG treatment following TBI significantly reduced neuronal apoptosis and autophagy, and increased functional recovery. These effects were correlated with a decrease in the protein expression levels of tumor necrosis factor α and interleukin-6. However, no significant changes were observed in the protein expression levels of glutamate transporter-1 in the brain cortex. The results of the present study provide in vivo evidence that RSG may exert neuroprotective effects via the inhibition of neuronal apoptosis and autophagy following experimental TBI in rats, and the mechanism underlying these effects may be associated with the anti-inflammatory action of RSG. The present study offers a novel insight into the potential use of RSG as a neuroprotective agent for the treatment of cerebral injuries.