Inhibition of neuronal peroxisome proliferator-activated receptor-γ attenuates motor function improvement after spinal cord injury in rats.

Traumatic spinal cord injury (SCI) causes secondary damage in injured and adjacent regions due to temporal deprivation of oxygen and energy supply. Peroxisome proliferator-activated receptor γ (PPARγ) is known to regulate cell survival mechanisms such as hypoxia, oxidative stress, inflammation and energy homeostasis in various tissues. Thus, PPARγ has the potential to show neuroprotective properties. However, the role of endogenous spinal PPARγ in SCI is not well established. In this study, under isoflurane inhalation, a 10-g rod was freely dropped onto the exposed spinal cord after T10 laminectomy using a New York University impactor in male Sprague-Dawley rats. Cellular localization of spinal PPARγ, locomotor function and mRNA levels of various genes including NFκB-targeted pro-inflammatory mediators after intrathecal administration of PPARγ antagonists, agonists or vehicles in SCI rats were then analysed. In both sham and SCI rats, spinal PPARγ was presented in neurons but not in microglia or astrocytes. Inhibition of PPARγ induced IκB activation and increased mRNA levels of pro-inflammatory mediators. It also suppressed recovery of locomotor function with myelin-related gene expression in SCI rats. However, a PPARγ agonist showed no beneficial effects on the locomotor performances of SCI rats, although it further increased the protein expression of PPARγ. In conclusion, endogenous PPARγ has a role in anti-inflammation after SCI. Inhibition of PPARγ might have a negative influence on motor function recovery through accelerated neuroinflammation. Nonetheless, exogenous PPARγ activation does not appear to effectively help with functional improvement after SCI.