Dynamic Changes in Brain Iron Metabolism in Neonatal Rats after Hypoxia-Ischemia

Hu, Ding-Wang; Zhao, Geng; Lin, Ling; Yu, Xuan-Jing; Wang, Rui; Lin, Qing

doi:10.1016/j.jstrokecerebrovasdis.2022.106352

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…The regulation between hypoxia and iron is complexed. On the one hand, hypoxia stress can cause iron homeostasis disorder (Aral et al, 2020;Hu et al, 2022); on the other hand, hypoxia is beneficial and can protect cells from death caused by abnormal iron metabolism (Ast et al, 2019;Fuhrmann et al, 2020;Ni et al, 2021). Our study also confirms that maintaining iron homeostasis is critical to respond to hypoxia stress.…”

Section: Discussionsupporting

confidence: 79%

Iron supplementation inhibits hypoxia-induced mitochondrial damage and protects zebrafish liver cells from death

et al. 2022

Front. Physiol.

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Acute hypoxia in water has always been a thorny problem in aquaculture. Oxygen and iron play important roles and are interdependent in fish. Iron is essential for oxygen transport and its concentration tightly controlled to maintain the cellular redox homeostasis. However, it is still unclear the role and mechanism of iron in hypoxic stress of fish. In this study, we investigated the role of iron in hypoxic responses of two zebrafish-derived cell lines. We found hypoxia exposed zebrafish liver cells (ZFL) demonstrated reduced expression of Ferritin and the gene fth31 for mitochondrial iron storage, corresponding to reduction of both intracellular and mitochondrial free iron and significant decrease of ROS levels in multiple cellular components, including mitochondrial ROS and lipid peroxidation level. In parallel, the mitochondrial integrity was severely damaged. Addition of exogenous iron restored the iron and ROS levels in cellular and mitochondria, reduced mitochondrial damage through enhancing mitophagy leading to higher cell viability, while treated the cells with iron chelator (DFO) or ferroptosis inhibitor (Fer-1) showed no improvements of the cellular conditions. In contrast, in hypoxia insensitive zebrafish embryonic fibroblasts cells (ZF4), the expression of genes related to iron metabolism showed opposite trends of change and higher mitochondrial ROS level compared with the ZFL cells. These results suggest that iron homeostasis is important for zebrafish cells to maintain mitochondrial integrity in hypoxic stress, which is cell type dependent. Our study enriched the hypoxia regulation mechanism of fish, which helped to reduce the hypoxia loss in fish farming.

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Section: Discussionsupporting

confidence: 79%

Iron supplementation inhibits hypoxia-induced mitochondrial damage and protects zebrafish liver cells from death

et al. 2022

Front. Physiol.

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“…Clinical studies have shown that obvious bleeding points appear in the periventricular white matter after WMI in newborns [11], and abnormal accumulation of iron content appears in the basal ganglia [12] while non-protein bound iron levels in the cerebrospinal fluid and serum are significantly increased [13]. Our previous study results also indicate that the iron content in the brains of neonatal rats increased significantly after HI [14]. The above results suggest that the iron metabolism changes may be involved in the occurrence and development of neonatal WMI, although the specific process and mechanism of abnormal iron metabolism are not completely understood.…”

Section: Introductionmentioning

confidence: 57%

“…Iron homeostasis was found to be upregulated and appeared to regulate myelin metabolism [ 28 ]. Our previous research also shows that changes in iron metabolism could affect myelination [ 14 ]. But it is still unclear how the abnormal iron metabolism occurred in the hypoxic-ischemic WMI.…”

Section: Discussionmentioning

confidence: 99%

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

Lin

Hao

et al. 2023

Neural Plasticity

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Hypoxic-ischemic white matter injury (WMI) pathogenesis in preterm infants is not well established, and iron-related proteins in the brain may play an important role in imbalanced iron metabolism. We aimed to investigate the iron-related protein changes in neonatal rats after hypoxia-ischemia (HI), clarify the role of iron-related proteins in hypoxic-ischemic WMI, and potentially provide a new target for the clinical treatment of hypoxic-ischemic WMI in preterm infants. We adopted a WMI animal model of bilateral common carotid artery electrocoagulation combined with hypoxia in neonatal 3-day-old Sprague-Dawley rats. We observed basic myelin protein (MBP) and iron-related protein expression in the brain (ferritin, transferrin receptor [TfR], and membrane iron transporter 1 [FPN1]) via Western blot and double immunofluorescence staining. The expression of MBP in the WMI group was significantly downregulated on postoperative days (PODs) 14, 28, and 56. Ferritin levels were significantly increased on PODs 3, 7, 14, and 28 and were most significant on POD 28, returning to the sham group level on POD 56. FPN1 levels were significantly increased on PODs 7, 28, and 56 and were still higher than those in the sham group on POD 56. TfR expression was significantly upregulated on PODs 1, 7, and 28 and returned to the sham group level on POD 56. Immunofluorescence staining showed that ferritin, TfR, and FPN1 were expressed in neurons, blood vessels, and oligodendrocytes in the cortex and corpus callosum on POD 28. Compared with the sham group, the immune-positive markers of three proteins in the WMI group were significantly increased. The expression of iron-related proteins in the brain (ferritin, FPN1, and TfR) showed spatiotemporal dynamic changes and may play an important role in hypoxic-ischemic WMI.

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“…Thiol is a very important antioxidant in preventing oxidative stress-induced damage and protects the cell against oxidative stress [41]. MDA is a major biomarker that appears during the nal stages of lipid peroxidation initiated by excessive ROS and indicates indirect impairment at the cellular levels [42]. Benincasa hispida treated with extracts signi cantly reserved the changes in CAT, GSH-Px, SOD, Total thiol, GPx, AOPP and MDA levels, suggesting that the neuroprotective effect of benincasa hispida scavenged ROS mainly by enhancing antioxidant activity and consequently decreasing lipid peroxidative damage.…”

Section: Groupmentioning

confidence: 99%

Benincasa Hispida Reversed D-galactose-induced oxidative Stress And Neurodegeneration-Mediated Cognitive Impairment In Aged Rats.

RC,

2023

Preprint

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Introduction: Age-related cognitive impairment is a common issue that is frequently brought on by oxidative stress and neurodegeneration in the brain. D-gal is a sugar moiety that has been linked to aging and cognitive disorders. This disease's prevalence is expected to rise linearly by 2050. Material & methods: Benincasa hispida, commonly known as wax gourd or winter melon, is a widely consumed vegetable with various medicinal properties. it belongs to the family of Cucurbitaceae. This study evaluates the neuroprotective role of a hydro-ethanolic seed extract of Benincasa hispida(BH) against D-gal-induced aging in rats. Healthy male rats were divided into six groups: The control group received normal saline, donepezil (2 mg/kg b.w.t., i.p.); D-gal (300 mg/kg b.w.t., i.p.); D-gal +BH (150 mg/kg b.w.t., o.p.); D-gal BH (250 mg/kg b.w.t., o.p.); and D-gal BH (300 mg/kg b.wt. Results and discussion: Behavioural, brain biochemical, and histopathological changes were assessed after treatment. The results of the behavioral study depicted that D-gal significantly reduces spontaneous alternation and locomotor activity, indicating behavioral and cognitive impairment. Biochemical studies showed that D-gal significantly increases oxidative stress in rat brains. Histopathological study showed that D-gal disturbs the normal architecture of hippocampal and cortical cells, indicating degeneration in these brain areas. D-gal and BH co-treatment for 42 days attenuated the behavioral, biochemical, and neuroanatomic damages caused by D-gal; it markedly suppressed the D-gal-induced oxidative stress and AChE activity in the brain and maintained the normal cellular architecture in hippocampal and cortical areas. Conclusion: Thus, this study shows that BH can protect the brain from the adverse effects of D-gal (e.g., memory loss and cognitive impairment) by modulating oxidative stress.

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Dynamic Changes in Brain Iron Metabolism in Neonatal Rats after Hypoxia-Ischemia

Cited by 8 publications

References 26 publications

Iron supplementation inhibits hypoxia-induced mitochondrial damage and protects zebrafish liver cells from death

Iron supplementation inhibits hypoxia-induced mitochondrial damage and protects zebrafish liver cells from death

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

Benincasa Hispida Reversed D-galactose-induced oxidative Stress And Neurodegeneration-Mediated Cognitive Impairment In Aged Rats.

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