Insights into the role of iron in immature rat model of hypoxic-ischemic brain injury

Abstract

This study aimed to investigate the role of iron in the occurrence and development of hypoxic-ischemic brain injury (HIBI) in immature rat models using 3-day-old Sprague Dawley rats. Normal control (NC), hypoxic-ischemic (HI), anemia, HI + ischemia, early iron treatment and late iron treatment groups were established. Rat brain tissue sections were stained with hematoxylin and eosin and pathologically evaluated. Iron content and mRNA expression levels of iron regulatory protein 2 (IRP2) and transferrin receptor in the brain tissues were measured. Ultrastructural changes in the actin, microtubules, myelin and mitochondria of oligodendrocytes and axons were examined by electron microscopy. Numbers of viable myelin sheaths and oligodendrocytes in the periventricular area were also observed. Pathological damage of brain tissue in the HI group was markedly increased compared with that in the NC group. Furthermore, there was a higher iron content and reduced number of viable oligodendrocytes in the periventricular area of the HI group compared with the NC group. No significant difference in iron content was observed between the HI + anemia and NC groups. The number of viable oligodendrocytes in the HI + anemia group was increased compared with that in the HI group, and the number in the HI + anemia group with late iron treatment was lower compared with that in the NC group and increased compared with that in the HI + anemia group. Electron microscopy revealed a significantly higher number of myelin sheaths in the HI + anemia group than in the HI group. IRP2 mRNA expression levels in the brain tissues were significantly decreased in the HI + anemia group compared with the HI group. The results suggest that anemia may reduce the rate of increase of iron content of the brain following HI. However, the early occurrence of anemia may protect against HIBI.

Effect of Hypoxia-Ischemia on the Expression of Iron-Related Proteins in Neonatal Rat Brains

“…As described in the study by Wang et al [ 22 ], the experimental WMI model in newborn SD rats was induced using the hypoxic-ischemic method or sham operation. Briefly, SD rats at P3 were anesthetized with isoflurane and were fixed on the operating table in a supine position, and the neck skin was disinfected with 75% alcohol.…”

N-Acetyl Serotonin Provides Neuroprotective Effects by Inhibiting Ferroptosis in the Neonatal Rat Hippocampus Following Hypoxic Brain Injury

“…As a type of cell death, ferroptosis can be induced by the inhibition of glutathione peroxidase 4 (GPX4) or the disruption of glutathione (GSH) synthesis; iron accumulation can exacerbate this process [10] . Researchers have shown that iron levels were increased in the brain tissue of neonatal HIBD patients [11] . In addition, some studies have shown that the prognosis of HIBD may be improved by desferrioxamine and erythropoietin, which modulate iron metabolism [12,13] .…”