Department of Physiology, University of Szeged, School of Medicine, Szeged, Hungary.
Curr Pharm Des. 2021;27(5):687-694. doi: 10.2174/1381612826666201113095720.
Hypoxic-ischemic encephalopathy (HIE) remains to be a major cause of morbidity, mortality and severe neurodevelopmental disability in term neonates. Moderate whole body hypothermia is an established, effective neuroprotective therapy to reduce mortality and long-term disability associated with HIE, however, research for adjunct therapies is still warranted to complement the effect of hypothermia. In the last decade, molecular hydrogen emerged as a simple, available, inexpensive substance with advantageous pharmacokinetics to ameliorate hypoxic-ischemic cellular damage. The present review examines the preclinical studies employing hydrogen to combat the deleterious consequences of hypoxic-ischemic insults in rodent and piglet HIE models. Hydrogen exerted unequivocal neuroprotective actions shown by preserved neurovascular function, neuronal viability, and neurocognitive functions in virtually all model species and hypoxic-ischemic insult types tested. Administration of hydrogen started in most studies after the hypoxic-ischemic insult enhancing the translational value of the findings. Among the explored mechanisms of hydrogen-induced neuroprotection, antioxidant, anti- apoptotic and anti-inflammatory effects appeared to be dominant. Unfortunately, the additive neuroprotective effect of hydrogen and therapeutic hypothermia has not yet been demonstrated, thus such studies are warranted to promote the clinical testing of molecular hydrogen as an adjunct neuroprotective treatment of HIE.
缺氧缺血性脑病（HIE）仍然是足月新生儿发病率、死亡率和严重神经发育残疾的主要原因。全身亚低温是一种已确立的、有效的神经保护治疗方法，可降低与 HIE 相关的死亡率和长期残疾，但仍需要研究辅助治疗方法来补充低温的作用。在过去十年中，分子氢作为一种简单、可用、廉价的物质，具有有利的药代动力学特性，可改善缺氧缺血性细胞损伤，引起了人们的关注。本综述检查了使用氢来对抗啮齿动物和小猪 HIE 模型中缺氧缺血性损伤的有害后果的临床前研究。氢在几乎所有的模型物种和缺氧缺血性损伤类型中都表现出明确的神经保护作用，表现为神经血管功能、神经元活力和神经认知功能的保留。在大多数研究中，氢的给药是在缺氧缺血性损伤后开始的，这提高了研究结果的转化价值。在氢诱导的神经保护作用的探索机制中，抗氧化、抗细胞凋亡和抗炎作用似乎占主导地位。不幸的是，氢和治疗性低温的附加神经保护作用尚未得到证实，因此需要进行此类研究，以促进将分子氢作为 HIE 的辅助神经保护治疗进行临床测试。
