2. Academic Validation
  3. Ferrostatin-1 attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis

Ferrostatin-1 attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting ferroptosis

  • Transl Pediatr. 2023 Nov 28;12(11):1944-1970. doi: 10.21037/tp-23-189.
Min Zhang 1 2 3 4,  Zhiming Liu 5,  Wei Zhou 1 2 3 4,  Ming Shen 1 2 3 4,  Niping Mao 1 2 3 4,  Hang Xu 6,  Yanan Wang 7,  Zidi Xu 7,  Mopu Li 7,  Haibin Jiang 7,  Yuetong Chen 6,  Jianghu Zhu 1 2 3 4,  Wei Lin 1 2 3 4,  Junhui Yuan 8,  Zhenlang Lin 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Pediatrics, the Second School of Medicine, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Key Laboratory of Perinatal Medicine of Wenzhou, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Key Laboratory of Structural Malformations in Children of Zhejiang Province, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 Zhejiang Provincial Clinical Research Center for Pediatric Disease, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 Department of Spinal Surgery, the Affiliated Hospital of Qingdao University, Qingdao, China.
  • 6 The First School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 7 The Second School of Medicine, Wenzhou Medical University, Wenzhou, China.
  • 8 Department of Neonatology, Wenling Maternal and Child Health Care Hospital, Wenling, China.
PMID: 38130589 DOI: 10.21037/tp-23-189
Abstract

Background: Hypoxic-ischemic brain damage (HIBD) is a type of brain damage that is caused by perinatal asphyxia and serious damages the central nervous system. At present, there is no effective drug for the treatment of this disease. Besides, the pathogenesis of HIBD remains elusive. While studies have shown that Ferroptosis plays an important role in HIBD, its role and mechanism in HIBD are yet to be fully understood.

Methods: The HIBD model of neonatal rats was established using the Rice-Vannucci method. A complete medium of PC12 cells was adjusted to a low-sugar medium, and the oxygen-glucose deprivation model was established after continuous hypoxia for 12 h. Laser Doppler blood flow imaging was used to detect the blood flow intensity after modeling. 2,3,5-triphenyl tetrazolium chloride staining was employed to detect ischemic cerebral infarction in rat brain tissue, and hematoxylin and eosin staining and transmission electron microscopy were used to observe brain injury and mitochondrial damage. Immunofluorescence was applied to monitor the expression of GFAP. Real-time quantitative polymerase chain reaction, western blot, and immunofluorescence were utilized to detect the expression of messenger RNA and protein. The level of Reactive Oxygen Species (ROS) in cells was detected using the ROS detection kit.

Results: The results showed that ferrostatin-1 (Fer-1) significantly alleviated the brain injury caused by hypoxia and ischemia. Fer-1 significantly increased the expression of SLC3A2, SLC7A11, ACSL3, GSS, and GPX4 (P<0.05) and dramatically decreased the expressions of GFAP, ACSL4, TFRC, FHC, FLC, 4-HNE, HIF-1α, and ROS (P<0.05).

Conclusions: Fer-1 inhibits Ferroptosis and alleviates HIBD by potentially targeting the GPX4/ACSL3/ACSL4 axis; however, its specific mechanism warrants further exploration.

Keywords

Ferroptosis; ferrostatin-1 (Fer-1); hypoxic-ischemic brain damage (HIBD); oxygen-glucose deprivation (OGD).

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