Systemic iron chelation results in limited functional and histological recovery after traumatic spinal cord injury in rats

Exp Neurol. 2013 Oct;248:53-61. doi: 10.1016/j.expneurol.2013.05.011. Epub 2013 May 24.

Abstract

Excess iron accumulation within the spinal cord is thought to exacerbate tissue damage and limit functional recovery after traumatic spinal cord injury (SCI). An optimal treatment to reverse or prevent damage would be to deliver an iron chelator systemically. Thus, we tested oral delivery of deferasirox (Exjade) in multiple studies using a rat model of mid-thoracic spinal contusion. Female Sprague-Dawley rats received a moderate contusion at vertebral level T8 and were given daily deferasirox for the first 7 or 14 days post-injury. The first two studies showed modest improvements in hindlimb function with limited improvement in tissue sparing. Two subsequent experiments to assess chronic functional changes and test longer-duration treatments failed to produce significant improvements. Testing a 2-fold higher deferasirox dose resulted in toxic side effects. To verify iron chelation treatment was effective, hepatic iron levels were measured which revealed that deferasirox robustly and significantly reduced systemic iron levels. Overall, this study suggests that oral iron chelation with deferasirox may lead to small but significant improvements in locomotor recovery or tissue sparing. However, given the lack of robust beneficial effects combined with potentially detrimental side effects such as exacerbated systemic anemia, oral administration of iron chelators may not be ideal for minimizing intraspinal iron-mediated pathology after SCI.

Keywords: Anemia; Ferritin; Hemorrhage; Macrophage; Myelin; Neuroprotection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Benzoates / pharmacology
  • Benzoates / therapeutic use*
  • Cervical Vertebrae
  • Deferasirox
  • Disease Models, Animal
  • Female
  • Iron Chelating Agents / pharmacology
  • Iron Chelating Agents / therapeutic use*
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*

Substances

  • Benzoates
  • Iron Chelating Agents
  • Triazoles
  • Deferasirox