Iron promotes neurological function recovery in mice with ischemic stroke through endogenous repair mechanisms

• Published in: Free radical biology & medicine 2022-03, Vol.182, p.59-72
• Main Authors: Guo, Xin, Jin, Xiaofang, Han, Kang, Kang, Shaomeng, Tian, Siyu, Lv, Xin, Feng, Mudi, Zheng, Huiwen, Zuo, Yong, Xu, Guodong, Hu, Ming, Xu, Jing, Lv, Peiyuan, Chang, Yan-zhong
• Format: Article
• Language: English
• Subjects: Animals; Brain Ischemia - drug therapy; Brain Ischemia - genetics; Brain Ischemia - metabolism; Gliosis; Infarction, Middle Cerebral Artery - drug therapy; Iron; Iron - metabolism; Ischemic Stroke; Mice; Mice, Inbred C57BL; Myelination; Nerve regeneration; Recovery of Function - physiology; Stroke - drug therapy; Stroke - metabolism; Synaptic plasticity
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2022.02.017

The endogenous repair mechanisms play an important role in the recovery of nerve function after stroke, such as gliosis, synaptic plasticity, remyelination and nerve regeneration. Iron is the most abundant trace metal element in the brain and plays a crucial role in the maintenance of normal cerebral function. It is an important coenzyme factor in the process of cell metabolism, DNA synthesis, purine catabolism and neurotransmitter synthesis and decomposition. However, it is unclear what role iron plays in the long-term recovery of neurological function after stroke. In this study, we first observed that changes in iron metabolism occurred during neurological function recovery in the mice with distal middle cerebral artery occlusion (dMCAO). Our data showed that plasticity changes due to endogenous repair mechanisms resulted in improvements in cerebral cortex function. These changes involved gliosis, synaptic function reconstruction, remyelination, and activation of neural stem cells. In order to examine the potential role of iron, we synthesized liposomal-encapsulated deferoxamine (DFO) nanoparticles to further explore the effect and the mechanism of iron on the recovery of neurological function in dMCAO mice. Our results showed that liposome-DFO decreased iron deposition and reversed plasticity changes in cerebral cortex function after stroke, which delayed neurological function recovery. This experiment shows that the increasing iron level promotes endogenous repair in ischemic stroke. Our finding reveals the change regularity of iron and emphasizes the beneficial role of iron in the recovery process of neurological function, which provides an important basis for the prevention and/or treatment of ischemia-reperfusion and recovery after stroke. [Display omitted] •Changes in iron metabolism occur during neurological function recovery after ischemic stroke. Iron level increases on Days 28 after ischemic stroke.•Gliosis, synaptic reconstruction, remyelination, and activation of neural stem cells participate in endogenous repair mechanisms after ischemic stroke.•Liposome-DFO nanoparticles reverse plasticity changes via reducing iron deposition and delay neurological function recovery after ischemic stroke.•The increasing iron level may promote endogenous repair in the recovery of ischemic stroke.