Translational Health Sciences, University of Bristol, Bristol, United Kingdom.
Department of Physiology, Institute of Basic Medical Research, University of Oslo, Oslo, Norway.
Ther Hypothermia Temp Manag. 2023 Dec;13(4):170-174. doi: 10.1089/ther.2023.0050. Epub 2023 Aug 28.
Posthypoxic therapeutic hypothermia has been tested in newborn infants, with seven randomized trials showing consistent evidence of reduction in death, cerebral palsy, and cognitive impairment at school age. In contrast, randomized trials of hypothermia after cardiac arrest in adults have not shown consistent evidence of lasting neurological protection. The apparently greater effectiveness of therapeutic hypothermia in newborns may be due to important biological and clinical differences. One such difference is that adults are heavily colonized with microbes, and many have active inflammatory processes at the time of arrest, but few newborns are heavily colonized or infected at the time of birth. Inflammation can interfere with hypothermia's neuroprotection. A second difference is that apoptosis is more commonly the pathway of neuronal death in newborns than in adults. Hypothermia inhibits apoptosis but not necrosis. Newborns have a larger endogenous supply of stem cells (which reduce apoptosis) than adults and this may favor regeneration and protection from hypothermia and regeneration. A third difference is that immature oligodendroglia are more sensitive to free radical attack then mature oligodendroglia. Hypothermia reduces free radical release. In addition, immature brain has increased N-methyl-D-aspartate receptor subunits compared with adults and hypothermia reduces excitotoxic amino acids. Adults suffering cardiac arrest often have comorbidities such as diabetes, hypertension, and atherosclerosis, which complicate recovery, but newborn infants rarely have comorbidities before asphyxia. Adult hypothermia treatment may have been too short as no trial has cooled for longer than 48 hours, some only 24 or 12 hours, but neonatal therapeutic hypothermia has routinely lasted 72 hours. We hypothesize that this combination of differences favors the effectiveness of therapeutic hypothermia in newborn infants compared with adults.
亚低温治疗已在新生儿中进行了试验，7 项随机试验一致表明可降低死亡率、脑瘫和学龄期认知障碍。相比之下，心脏骤停后成人亚低温治疗的随机试验并未一致证明有持久的神经保护作用。亚低温治疗在新生儿中更有效的效果可能是由于重要的生物学和临床差异所致。其中一个差异是，成人的微生物定植严重，许多人在发生心脏骤停时存在活跃的炎症过程，但很少有新生儿在出生时严重定植或感染。炎症会干扰亚低温的神经保护作用。另一个差异是，凋亡是新生儿神经元死亡的常见途径，而不是成人。亚低温抑制凋亡而不抑制坏死。新生儿的内源性干细胞供应（减少凋亡）比成人多，这可能有利于再生和免受亚低温和再生的影响。第三个差异是，未成熟少突胶质细胞比成熟少突胶质细胞更容易受到自由基攻击。亚低温可减少自由基的释放。此外，未成熟的大脑比成人具有更多的 N-甲基-D-天冬氨酸受体亚基，而亚低温可减少兴奋性氨基酸。发生心脏骤停的成人常患有糖尿病、高血压和动脉粥样硬化等合并症，这会使恢复复杂化，但新生儿在窒息前很少有合并症。成人亚低温治疗可能时间过短，因为没有一项试验的冷却时间超过 48 小时，有些试验只有 24 或 12 小时，但新生儿的亚低温治疗通常持续 72 小时。我们假设，这种差异的组合有利于亚低温治疗在新生儿中的有效性，而不是在成人中。
