Attenuation of White Matter Damage Following Deferoxamine Treatment in Rats After Spinal Cord Injury

• Published in: World neurosurgery Vol. 137; pp. e9 - e17
• Main Authors: Shi, Jiantao, Tang, Rongrui, Zhou, Yi, Xian, Jishu, Zuo, Chenghai, Wang, Long, Wang, Jie, Feng, Hua, Hu, Shengli
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2020
• Subjects: Deferoxamine; Demyelination; Iron overload; Spinal cord injury; Iron overload; PBS; APP; TfR; BBB; DMT1; i.p; Spinal cord injury; Deferoxamine; ICH; Demyelination; DFX; SCI; dMBP; TEM
• ISSN: 1878-8750; 1878-8769
• DOI: 10.1016/j.wneu.2019.08.246

With little information available on axonal and myelin damage surrounding the contusion, the study of spinal cord injury (SCI) so far has focused on neuronal death. In this study, we investigated the role of iron overload in long-term oligodendroglia death and progressive white matter damage to rats after SCI using the iron chelator, deferoxamine (DFX).
Female Sprague-Dawley rats received either a contusion at T10 or sham-surgery. The rats were treated with DFX or vehicle. All rats were evaluated in behavioral assessments and then euthanized at different time points. Spinal cords were analyzed by diaminobenzidine-enhanced Perls' staining, non-heme iron measurements, Western blotting, immunohistochemistry, and transmission electron microscopy.
Iron accumulation after SCI resulted in the upregulation of transferrin receptor and divalent metal transporter 1, which exacerbated the intracellular iron overload. DFX treatment reduced iron overload–induced delayed oligodendrocyte death (e.g., 21 days: 47.12 ± 10.5 vs. 20.02 ± 9.4 x 103/mm2 in the vehicle-treated group, n = 4, P < 0.05). After SCI, the markers of axonal damage and demyelination were increased in white matter in the vehicle-treated group compared with the DFX-treated group (P < 0.05).
Iron overload plays an important role in progressive white matter damage after SCI. DFX may be an effective treatment for white matter damage after SCI.