Peroxisome proliferator-activated receptor-γ agonist rosiglitazone reduces secondary damage in experimental spinal cord injury

J Int Med Res. 2013 Feb;41(1):153-61. doi: 10.1177/0300060513476601. Epub 2013 Jan 24.

Abstract

Objective: To investigate the neuroprotective effects of rosiglitazone in a rat traumatic spinal cord injury (SCI) model.

Methods: Adult Sprague-Dawley rats (n = 12/group) underwent laminectomy (sham), SCI, SCI and rosiglitazone treatment (2 mg/kg twice daily for 7 days), or SCI and saline injection (vehicle). SCI was induced via dural application of an aneurysm clip. Spinal cord apoptosis and levels of tumour necrosis factor-α (TNFα), interleukin (IL)-1β, myeloperoxidase (MPO) and the apoptosis-associated proteins B-cell leukaemia/lymphoma 2 (Bcl-2) and Bcl-2 associated X protein (Bax) were examined 24 h after SCI. Locomotor function was evaluated 3, 7, 10, 14 and 21 days after SCI.

Results: At 24 h after SCI, apoptosis and TNFα, IL-1β and MPO concentrations were significantly lower in the rosiglitazone group than in the vehicle and SCI groups. SCI resulted in an increase in Bax and a decrease in Bcl-2, which was reversed by rosiglitazone treatment. Rats in the rosiglitazone group had significantly better functional recovery than those in the vehicle and SCI groups.

Conclusion: Rosiglitazone significantly improved functional recovery, probably via attenuation of the local inflammatory reaction and reduced apoptosis.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Interleukin-1beta / metabolism
  • Male
  • Motor Activity / drug effects
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Rosiglitazone
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology*
  • Spinal Cord Injuries / physiopathology
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-2-Associated X Protein / metabolism

Substances

  • Interleukin-1beta
  • PPAR gamma
  • Thiazolidinediones
  • Tumor Necrosis Factor-alpha
  • bcl-2-Associated X Protein
  • Rosiglitazone
  • Peroxidase