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

IF 4.6 2区医学 Q1 NEUROSCIENCES

Experimental Neurology Pub Date : 2025-04-15 DOI:10.1016/j.expneurol.2025.115262

Qiyi Huang , Jiahang Tang , You Xiang , Xinying Shang , Kunlin Li , Lijia Chen , Junnan Hu , Han Li , Yanxiong Pi , Haiyan Yang , Huijia Zhang , Heng Tan , Yanbin Xiyang , Huiyan Jin , Xia Li , Manjun Chen , Rongrong Mao , Qian Wang

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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.

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4-苄基-2-甲基-1,2,4-噻二唑烷-3,5-二酮可挽救导致髓鞘脱失的少突胶质细胞铁突变，改善神经元损伤，促进新生儿缺氧缺血性脑损伤的记忆

新生儿脑缺氧缺血（HI）可引起脑白质损伤（WMI），导致行为障碍。髓磷脂是由易受缺氧缺血（HI）影响的少突胶质细胞形成的，具有调节运动和认知功能的功能，容易被缺氧损伤而导致髓磷脂丢失。4-苄基-2-甲基-1,2,4-噻二唑烷-3,5-二酮（TDZD-8）在HI后神经元死亡中具有潜在的拯救作用。研究报告神经元铁下垂可由HI引起，并与行为异常有关。然而，TDZD-8对WMI的影响及其与记忆恢复的关系尚不清楚。在本研究中，我们的HIBD模型显示由神经元损伤和髓磷脂丢失引起的记忆功能受损。TDZD-8有效地逆转了这种病理。潜在的机制探索表明，TDZD-8通过铁下沉途径改善髓磷脂损失参与了TDZD-8治疗新生儿HIBD的过程。总之，我们的数据表明，白质修复和神经元保护的联合作用实现了TDZD-8在新生儿HIBD中的治疗作用，提示白质修复也可以成为新生儿HIBD的一种重要的临床治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Neurology 医学-神经科学

CiteScore

10.10

自引率

3.80%

发文量

258

审稿时长

42 days

期刊介绍： Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.