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Decrease of PPARδ in Type-1-Like Diabetic Rat for Higher Mortality after Spinal Cord Injury.

Cheng-Chia Tsai1, Kung-Shing Lee2, Sheng-Hsien Chen3

  • 1Department of Neurosurgery, Mackay Memorial Hospital, Taipei City 10449, Taiwan ; Graduate Institute of Injury Prevention and Control, Taipei Medical University, Taipei City 10401, Taiwan.

PPAR Research
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Diabetes worsens spinal cord injury (SCI) outcomes, linked to reduced peroxisome proliferator-activated receptors- δ (PPAR δ) expression. PPAR δ activation improved survival and function in diabetic rats post-SCI.

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Area of Science:

  • Neuroscience
  • Metabolic Disorders
  • Pharmacology

Background:

  • Spinal cord injury (SCI) outcomes are poorer in diabetic individuals.
  • Peroxisome proliferator-activated receptors- δ (PPAR δ) expression changes post-SCI, but its role in diabetic SCI is unclear.

Purpose of the Study:

  • To investigate the relationship between diabetes progression and PPAR δ expression in rats following SCI.
  • To evaluate the therapeutic potential of a PPAR δ agonist (GW0742) in diabetic rats with SCI.

Main Methods:

  • Compressive SCI was induced in streptozotocin (STZ)-induced diabetic rats.
  • PPAR δ expression was measured using Western blot.
  • Survival rates, motor function, and pain response were assessed.
  • Treatment with PPAR δ agonist (GW0742) and antagonist (GSK0660) was administered.

Main Results:

  • STZ-diabetic rats exhibited lower PPAR δ expression in spinal cords compared to controls.
  • Survival time decreased with longer diabetes duration (8 weeks vs. 2 weeks).
  • GW0742 significantly improved survival time, motor function, and pain response in diabetic rats post-SCI.
  • GSK0660 worsened motor function and pain response.

Conclusions:

  • Reduced PPAR δ expression correlates with increased mortality in diabetic rats after SCI.
  • Diabetes progression exacerbates SCI severity, potentially via decreased PPAR δ expression.
  • Targeting PPAR δ with agonists like GW0742 may offer a therapeutic strategy for SCI in diabetic patients.