Gunn A J, Bennet L, Gunning M I, Gluckman P D, Gunn T R
Research Centre for Developmental Medicine and Biology, Faculty of Medicine and Health Science, The University of Auckland, New Zealand.
Pediatr Res. 1999 Sep;46(3):274-80. doi: 10.1203/00006450-199909000-00005.
Prolonged cerebral hypothermia is neuroprotective if started within a few hours of hypoxia-ischemia. However, delayed seizure activity is one of the major clinical indicators of an adverse prognosis after perinatal asphyxia. The aim of this study was to determine whether head cooling delayed until after the onset of postasphyxial seizures may still be neuroprotective. Unanesthetized near-term fetal sheep in utero received 30 min of cerebral ischemia induced by bilateral carotid artery occlusion. Eight and one-half hours later, they received either cooling (n = 5) or sham cooling (n = 13) until 72 h after the insult. Intrauterine cooling, induced by circulating cold water through a coil around the fetal head, was titrated to reduce fetal extradural temperature from 39.4+/-0.1 degrees C to between 30 and 33 degrees C. Cerebral ischemia led to the delayed development of intense epileptiform activity from 6 to 8 h postinsult, followed by a marked secondary rise in cortical impedance (a measure of cytotoxic edema) and in carotid blood flow. Cerebral cooling markedly attenuated the secondary rise in impedance and reduced carotid blood flow (p < 0.001). After 5 d recovery, there was no significant difference in loss of parietal EEG activity relative to baseline in the hypothermia compared with the control group (-12.5+/-1.4 versus -15.2+/-1.2 dB, mean +/- SEM, NS) or in parasagittal cortical neuronal loss (82+/-9 versus 90+/-5%, NS). In conclusion, delayed prolonged head cooling begun after the onset of postischemic seizures was not neuroprotective. These data highlight the importance of intervention in the latent phase, after reperfusion but before the onset of secondary injury.
如果在缺氧缺血后的数小时内开始进行长时间的脑部低温治疗，具有神经保护作用。然而，延迟性癫痫活动是围产期窒息后不良预后的主要临床指标之一。本研究的目的是确定延迟至窒息后癫痫发作开始后才进行头部降温是否仍具有神经保护作用。未麻醉的近足月宫内胎羊接受双侧颈动脉闭塞诱导的30分钟脑缺血。8.5小时后，它们接受降温治疗（n = 5）或假降温治疗（n = 13），持续至损伤后72小时。通过环绕胎头的盘管循环冷水来诱导宫内降温，调节温度使胎儿硬膜外温度从39.4±0.1℃降至30至33℃之间。脑缺血导致损伤后6至8小时出现强烈的癫痫样活动延迟发展，随后皮质阻抗（细胞毒性水肿的一种测量指标）和颈动脉血流显著继发性升高。脑部降温明显减轻了阻抗的继发性升高并降低了颈动脉血流（p < 0.001）。恢复5天后，与对照组相比，低温治疗组顶叶脑电图活动相对于基线的损失无显著差异（-12.5±1.4对-15.2±1.2 dB，平均值±标准误，无显著性差异），矢状旁皮质神经元损失也无显著差异（82±9对90±5%，无显著性差异）。总之，缺血后癫痫发作开始后开始的延迟性长时间头部降温没有神经保护作用。这些数据突出了在再灌注后但在继发性损伤开始前的潜伏期进行干预的重要性。
