Authors
Youcheng Qin, Peilun Xiao, Xinyue Zhang, Zhigang Yang, Wenjie Xiang, Xiaozu Zhang, Haimo Zhang, Yanyu Zeng, Miao Yu, Yan Li, Jing Sui, Xiaoli Wang
Published in
Neuroreport. Aug 18, 2026. Epub Aug 18, 2026.
Abstract
This study aimed to elucidate the neuroprotective mechanism of melatonin (Mel) against hypoxic-ischemic brain damage (HIBD) in neonatal rats, specifically through the thioredoxin-interacting protein (TXNIP)/thioredoxin-1 (Trx-1)/glutathione peroxidase 4 (GPX4) pathway in neuronal ferroptosis, and to concurrently evaluate its therapeutic efficacy using multimodal MRI.
A neonatal rat HIBD model was established with pre- and postmodeling Mel administration. Neuroprotective effects were dynamically assessed in vivo via multimodal MRI. Hippocampal tissues were analyzed for ferroptosis markers and pathway components. In vitro, PC12 cells underwent oxygen-glucose deprivation (OGD) with or without Mel. TXNIP-overexpressing cells were used to verify the axis's specific role.
MRI confirmed that Mel significantly reduced infarct volume and improved cerebral blood flow (all P < 0.05). It preserved neuronal and mitochondrial integrity. Molecularly, Mel restored GPX4/Trx-1 and suppressed acyl-CoA synthetase long-chain family member 4/TXNIP (all P < 0.05). These effects were replicated in OGD-PC12 cells and persisted in TXNIP-overexpressing cells, supporting the involvement of this pathway.
Mel attenuates acute neonatal HIBD and reduces ferroptosis-associated neuronal injury, potentially involving modulation of the TXNIP/Trx-1/GPX4 pathway. Multimodal MRI may serve as a useful in-vivo tool for evaluating therapeutic responses after neonatal HIBD.
PMID:
42689393
Bibliographic data and abstract were imported from PubMed on 03 Sep 2026.
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