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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

Electron microscope snapshots of the axons, myelin and mitochondria in the rat brains (magnification, ×20,000). (A) In the normal control (NC) group, normal axons were observed. The arrows point to the axon filament microtubules. (B) Mitochondria in the NC group: The arrows indicate the ridge structure in the mitochondria, which exhibit a clear and complete shape. (C) In the hypoxic-ischemic (HI) group, the axonal microtubules and filaments were fractured and reduced in number (arrows). (D) Mitochondria in the HI group: The arrows indicate an increase in electron density, fractionation and disappearance of the ridges in the mitochondria. Scale bar, 1 µm.
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f3-etm-0-0-3550: Electron microscope snapshots of the axons, myelin and mitochondria in the rat brains (magnification, ×20,000). (A) In the normal control (NC) group, normal axons were observed. The arrows point to the axon filament microtubules. (B) Mitochondria in the NC group: The arrows indicate the ridge structure in the mitochondria, which exhibit a clear and complete shape. (C) In the hypoxic-ischemic (HI) group, the axonal microtubules and filaments were fractured and reduced in number (arrows). (D) Mitochondria in the HI group: The arrows indicate an increase in electron density, fractionation and disappearance of the ridges in the mitochondria. Scale bar, 1 µm.

Mentions: In the rat brains of the NC group a uniform thickness and density, as well as a regular shape and clear boundaries of the myelin sheath, were observed in the intact structure. Furthermore, the nerve cells had a refined structure, the organelles in the cytoplasm appeared to have a normal morphology, the mitochondrial structure was intact, the distribution of chromatin in the nucleus was uniform, the axonal microtubules and filaments were well-organized and integrity of structure was detected. In addition, no pathological changes were observed in the surrounding areas of the brain (Fig. 3A and B).


Insights into the role of iron in immature rat model of hypoxic-ischemic brain injury
Electron microscope snapshots of the axons, myelin and mitochondria in the rat brains (magnification, ×20,000). (A) In the normal control (NC) group, normal axons were observed. The arrows point to the axon filament microtubules. (B) Mitochondria in the NC group: The arrows indicate the ridge structure in the mitochondria, which exhibit a clear and complete shape. (C) In the hypoxic-ischemic (HI) group, the axonal microtubules and filaments were fractured and reduced in number (arrows). (D) Mitochondria in the HI group: The arrows indicate an increase in electron density, fractionation and disappearance of the ridges in the mitochondria. Scale bar, 1 µm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998421&req=5

f3-etm-0-0-3550: Electron microscope snapshots of the axons, myelin and mitochondria in the rat brains (magnification, ×20,000). (A) In the normal control (NC) group, normal axons were observed. The arrows point to the axon filament microtubules. (B) Mitochondria in the NC group: The arrows indicate the ridge structure in the mitochondria, which exhibit a clear and complete shape. (C) In the hypoxic-ischemic (HI) group, the axonal microtubules and filaments were fractured and reduced in number (arrows). (D) Mitochondria in the HI group: The arrows indicate an increase in electron density, fractionation and disappearance of the ridges in the mitochondria. Scale bar, 1 µm.
Mentions: In the rat brains of the NC group a uniform thickness and density, as well as a regular shape and clear boundaries of the myelin sheath, were observed in the intact structure. Furthermore, the nerve cells had a refined structure, the organelles in the cytoplasm appeared to have a normal morphology, the mitochondrial structure was intact, the distribution of chromatin in the nucleus was uniform, the axonal microtubules and filaments were well-organized and integrity of structure was detected. In addition, no pathological changes were observed in the surrounding areas of the brain (Fig. 3A and B).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus