title: Systemic iron chelation results in limited functional and histological recovery after traumatic spinal cord injury in rats.
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.
authors.affiliation: The Center for Brain and Spinal Cord Repair, The Ohio State University, Columbus, OH, USA; Department of Neuroscience, The Ohio State University, Columbus, OH, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Sauerbeck
authors.forename: David L
authors.initials: DL
authors.lastname: Schonberg
authors.forename: James L
authors.initials: JL
authors.lastname: Laws
authors.forename: Dana M
authors.initials: DM
authors.lastname: McTigue
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology / Q000627:therapeutic use*; D002574:Cervical Vertebrae; D000077588:Deferasirox; D004195:Disease Models, Animal; D005260:Female; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001565:Benzoates; D007502:Iron Chelating Agents; D014230:Triazoles; D000077588:Deferasirox
keywords: Anemia; Ferritin; Hemorrhage; Macrophage; Myelin; Neuroprotection