Inhibition of neuronal peroxisome proliferator-activated receptor-gamma attenuates motor function improvement after spinal cord injury in rats
EUROPEAN JOURNAL OF NEUROSCIENCE(2023)
Abstract
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 gamma (PPAR gamma) is known to regulate cell survival mechanisms such as hypoxia, oxidative stress, inflammation and energy homeostasis in various tissues. Thus, PPAR gamma has the potential to show neuroprotective properties. However, the role of endogenous spinal PPAR gamma 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 PPAR gamma, locomotor function and mRNA levels of various genes including NF kappa B-targeted pro-inflammatory mediators after intrathecal administration of PPAR gamma antagonists, agonists or vehicles in SCI rats were then analysed. In both sham and SCI rats, spinal PPAR gamma was presented in neurons but not in microglia or astrocytes. Inhibition of PPAR gamma induced I kappa B 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 PPAR gamma agonist showed no beneficial effects on the locomotor performances of SCI rats, although it further increased the protein expression of PPAR gamma. In conclusion, endogenous PPAR gamma has a role in anti-inflammation after SCI. Inhibition of PPAR gamma might have a negative influence on motor function recovery through accelerated neuroinflammation. Nonetheless, exogenous PPAR gamma activation does not appear to effectively help with functional improvement after SCI.
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Key words
anti-inflammation, motor function recovery, neuronal cell death, PPAR-gamma, spinal cord injury
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