PPAR-α modulate the anti-inflammatory effect of glucocorticoids in the secondary damage in experimental spinal cord trauma

Abstract

Glucocorticoids (GCs) are effective anti-inflammatory agents widely used in therapeutic approach to treatment of spinal cord trauma. Previous results suggest that peroxisome proliferator activated receptor alpha (PPAR-α), an intracellular transcription factor activated by fatty acids, plays a role in control of secondary inflammatory process associated with spinal cord injury (SCI). With the aim to characterize the role of PPAR-α in GC-mediated anti-inflammatory activity, we tested the efficacy of dexamethasone (DEX), a synthetic GC specific for glucocortioid receptor (GR), in an experimental model of spinal cord trauma induced in mice by the application of vascular clips (force of 24 g) to the dura via a four-level T5–T8 laminectomy, and comparing mice lacking PPAR-α (PPAR-αKO) with wild type (WT) mice. Results indicate that DEX-mediated anti-inflammatory activity is weakened in PPAR-αKO mice, as compared to WT controls. In particular, DEX was less effective in PPAR-αKO, compared to WT mice, as evaluated by inhibition of the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, nitrotyrosine formation, pro-inflammmatory cytokine expression, NF-κB activation, inducible nitric-oxide synthase (iNOS) expression; and apoptosis. This study indicates that PPAR-α can contribute to the anti-inflammatory activity of GCs in SCI.