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Updated: Jun 26, 2025
The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Menaquinone-4 alleviates hypoxic-ischemic brain damage in neonatal rats by reducing mitochondrial dysfunction via
Xiaoli Feng1, Yihui Zheng1, Niping Mao1
1Department of Neonatology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Perinatal Medicine of Wenzhou, Wenzhou, Zhejiang 325027, China.
Background:
Hypoxic-ischemic encephalopathy (HIE) is a major contributor to neonatal mortality and neurodevelopmental disorders, but currently there is no effective therapy drug for HIE. Mitochondrial dysfunction plays a pivotal role in hypoxic-ischemic brain damage(HIBD). Menaquinone-4 (MK-4), a subtype of vitamin K2 prevalent in the brain, has been shown to enhance mitochondrial function and exhibit protective effects against ischemia-reperfusion injury. However, the impact and underlying molecular mechanism of MK-4 in HIE have not been fully elucidated.
Methods:
In this study, we established the neonatal rats HIBD model in vivo and oxygen-glucose deprivation and reperfusion (OGD/R) of primary neurons in vitro to explore the neuroprotective effects of MK-4 on HI damage, and illuminate the potential mechanism.
Results:
Our findings revealed that MK-4 ameliorated mitochondrial dysfunction, reduced oxidative stress, and prevented HI-induced neuronal apoptosis by activating the Sirt1-PGC-1α-TFAM signaling pathway through Sirt1 mediation. Importantly, these protective effects were partially reversed by EX-527, a Sirt1 inhibitor.
Conclusion:
Our study elucidated the potential therapeutic mechanism of MK-4 in neonatal HIE, suggesting its viability as an agent for enhancing recovery from HI-induced cerebral damage in newborns. Further exploration into MK-4 could lead to novel interventions for HIE therapy.
