PPAR-γ agonist rosiglitazone reduces autophagy and promotes functional recovery in experimental traumaticspinal cord injury.

Background: Secondary damage is often more important in determining the functional outcome and provides a practical target for therapeutic intervention. Rosiglitazone (ROSG) is a potent PPAR-γ agonist and has been shown to induce neuroprotection in animal models of spinal cord injury (SCI). However, it is still unclear whether this PPAR-γ agonist can mediate neuronal autophagy after SCI.

Methods: SCI was induced by application of vascular clips (force of 24g) to the dura via a four-level T5-T8 laminectomy. The role of the PPAR-γ agonist ROSG on neuronal autophagy induced by SCI was investigated.

Results: The expression of autophagy-related proteins, including microtubule-associated protein 1 light chain 3 type II (LC3-II), beclin-1, and cathepsin D, increased significantly after SCI. ROSG downregulated autophagy-related protein expression and improved the locomotor function after SCI. GW9662 (a PPAR-γ inhibitor) significantly antagonized the effect of ROSG and abolished the protective effect on SCI.

Conclusions: Our results clearly demonstrated that the administration of ROSG after SCI reduced autophagy and promoted functional recovery after SCI in rats.