Gunn Alistair Jan, Battin Malcolm, Gluckman Peter D, Gunn Tania R, Bennet Laura
University of Auckland, Auckland, New Zealand.
J Perinat Med. 2005;33(4):340-6. doi: 10.1515/JPM.2005.061.
The possibility of a therapeutic role for cerebral hypothermia during or after resuscitation from perinatal asphyxia has been a long-standing focus of research. However, early studies had limited and contradictory results. It is now known that severe hypoxia-ischemia may not cause immediate cell death, but may precipitate a complex biochemical cascade leading to the delayed development of neuronal loss. These phases include a latent phase after reperfusion, with initial recovery of cerebral energy metabolism but EEG suppression, followed by a secondary phase characterized by accumulation of cytotoxins, seizures, cytotoxic edema, and failure of cerebral oxidative metabolism from 6 to 15 h post insult. Although many of the secondary processes can be injurious, they appear to be primarily epiphenomena of the 'execution' phase of cell death. This conceptual framework allows a better understanding of the experimental parameters that determine effective hypothermic neuroprotection, including the timing of initiation of cooling, its duration and the depth of cooling attained. Moderate cerebral hypothermia initiated in the latent phase, between one and as late as 6 h after reperfusion, and continued for a sufficient duration in relation to the severity of the cerebral injury, has been consistently associated with potent, long-lasting neuroprotection in both adult and perinatal species. The results of the first large multicentre randomized trial of head cooling for neonatal encephalopathy and previous phase I and II studies now strongly suggest that prolonged cerebral hypothermia is both generally safe - at least in an intensive care setting - and can improve intact survival up to 18 months of age. Both long-term followup studies and further large studies of whole body cooling are in progress.
围产期窒息复苏期间或之后进行脑低温治疗的可能性一直是长期的研究重点。然而，早期研究结果有限且相互矛盾。现在已知，严重的缺氧缺血可能不会导致立即的细胞死亡，而是可能引发复杂的生化级联反应，导致神经元损失的延迟发展。这些阶段包括再灌注后的潜伏期，此时脑能量代谢初步恢复但脑电图受抑制，随后是第二阶段，其特征是细胞毒素积累、癫痫发作、细胞毒性水肿以及损伤后6至15小时脑氧化代谢衰竭。尽管许多继发过程可能具有损伤性，但它们似乎主要是细胞死亡“执行”阶段的附带现象。这一概念框架有助于更好地理解决定有效低温神经保护的实验参数，包括开始降温的时间、持续时间以及达到的降温深度。在潜伏期，即再灌注后1至6小时之间开始的适度脑低温，并根据脑损伤的严重程度持续足够长的时间，在成年和围产期动物中一直与强大、持久的神经保护作用相关。第一项针对新生儿脑病头部降温的大型多中心随机试验以及之前的I期和II期研究结果现在强烈表明，延长的脑低温总体上是安全的——至少在重症监护环境中如此——并且可以提高18个月龄时的完整存活率。长期随访研究和关于全身降温的进一步大型研究正在进行中。
