2. Academic Validation
  3. 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione rescues oligodendrocytes ferroptosis leading to myelin loss and ameliorates neuronal injury facilitating memory in neonatal hypoxic-ischemic brain damage

4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione rescues oligodendrocytes ferroptosis leading to myelin loss and ameliorates neuronal injury facilitating memory in neonatal hypoxic-ischemic brain damage

  • Exp Neurol. 2025 Aug:390:115262. doi: 10.1016/j.expneurol.2025.115262.
Qiyi Huang 1,  Jiahang Tang 1,  You Xiang 1,  Xinying Shang 2,  Kunlin Li 1,  Lijia Chen 1,  Junnan Hu 1,  Han Li 1,  Yanxiong Pi 1,  Haiyan Yang 1,  Huijia Zhang 1,  Heng Tan 1,  Yanbin Xiyang 3,  Huiyan Jin 4,  Xia Li 1,  Manjun Chen 5,  Rongrong Mao 6,  Qian Wang 7
Affiliations

Affiliations

  • 1 Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China.
  • 2 Department of Emergency Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
  • 3 Institution of Neuroscience, Kunming Medical University, Kunming 650500, China.
  • 4 Department of Functional Experiment, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China.
  • 5 Department of Thoracic Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming 650500, China.
  • 6 Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China. Electronic address: talktomaomao@163.com.
  • 7 Department of Pathology and Pathophysiology, Faculty of Basic Medical Sciences, Kunming Medical University, Kunming 650500, China. Electronic address: 71132127@qq.com.
PMID: 40246011 DOI: 10.1016/j.expneurol.2025.115262
Abstract

Neonatal brain hypoxia-ischemia (HI) is proved to cause white matter injury (WMI), which resulted in behavioral disturbance. Myelin formed by oligodendrocytes vulnerable to hypoxia-ischemia (HI), regulating motor and cognitive function, is easily damaged by HI causing myelin loss. 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8) has a potential rescue role in neuronal death post HI. Studies reported that neuronal Ferroptosis could be induced by HI and linked to behavioral abnormalities. However, the effect of TDZD-8 on WMI and its involvement in memory recovery remains unclear. In this study, our HIBD model showed impaired memory function caused by neuronal injury and myelin loss. TDZD-8 effectively reversed this pathology. Underlying mechanistic exploration implied that TDZD-8 ameliorating myelin loss via Ferroptosis pathway was involved in the process of TDZD-8 treating neonatal HIBD. In conclusion, our data demonstrated that combined effect of white matter repairment and neuronal protection achieved the therapeutic role of TDZD-8 in neonatal HIBD, and suggested that white matter repairment also could be a considerable clinical therapy for neonatal HIBD.

Keywords

Ferroptosis; HIBD; Myelin; Neonatal mice; Oligodendrocytes.

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