Targeting the peroxisome proliferator-activated receptors (PPARs) in spinal cord injury.

摘要

INTRODUCTION: Traumatic spinal cord injury (SCI) causes severe and permanent functional deficits, due to the primary mechanical insult, followed by secondary tissue degeneration. The direct damage is followed by a second phase of tissue degeneration, which may take place over a period of weeks or even months, causing neuronal and axonal destruction. A key mediator of this process is an acute and robust inflammatory response, which involves the synthesis and release of chemokines and cytokines, and a coordinated recruitment of circulating leucocytes, as well as microglia, from the CNS parenchyma. The search for a 'cure' for SCI has yet to produce a convincingly efficacious treatment that improves the outcome for patients. AREAS COVERED: This review explores the experimental studies describing the beneficial effects of PPAR receptor modulators in spinal cord trauma. EXPERT OPINION: Because of safety issues and limited data, PPAR agonists are not yet included in SCI-related treatment strategies. PPAR agonists for specific isoforms (alpha, beta/delta and gamma) have demonstrated both anti-inflammatory and immunomodulatory properties. Pharmacological activation of PPAR can be considered as a multi-faceted therapeutic target, due to its anti-inflammatory/antioxidant/anti-excitotoxic/pro-energetic profile, reported in some neurological and inflammatory-related diseases.