Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep
Neuroprotection with prolonged head cooling started before postischemic seizures in fetal sheep
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DOI：
10.1542/peds.102.5.1098
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发表时间：
1998-11-01
期刊：
影响因子：
8
通讯作者：
Gluckman, PD
中科院分区：
文献类型：
--
作者：
Gunn, AJ;Gunn, TR;Gluckman, PD
Objective.脑低温已被证明，如果在再灌注后不久开始，可以减少实验性缺氧缺血造成的损伤。然而，在新生儿中，在暴露于窒息后这么快就确定预后可能是不可行的。本研究的目的是确定是否头部冷却，延迟到窒息后癫痫发作活动开始前不久，是神经保护。对子宫内未麻醉的近足月胎羊进行30分钟的脑缺血。随后，在5.5小时时，将其随机分配至冷却组（n = 7）或假冷却组（n = 10），持续72小时。通过绕胎头的线圈循环冷水来诱导宫内冷却。调整水温使胎儿硬膜外温度从39.1 ± 0.1 ℃降至30 ℃ ~ 33 ℃，同时保持食管温度>37 ℃。大脑冷却抑制皮层阻抗（细胞毒性水肿的测量）的二次上升，但不能防止延迟癫痫发作，缺血后8至30小时。观察到一过性代谢变化，包括血浆乳酸盐和葡萄糖水平升高以及血压中度持续升高。这种严重的大脑损伤导致5天恢复后残留顶叶脑电图活动降低（-14.2 +/-1.5分贝），与神经元损失的分水岭分布相关（腿，94 +/-4%在侧皮层，77 +/-4%在侧皮层）。低温与更好的脑电图活动恢复（-8.9% +/- 1.8分贝）和显著减少的旁皮层（46 +/- 13%）、外侧皮层（9 +/- 4%）和除海马区第1和第2区外的其他区域的神经元损失相关。在缺血后癫痫发作前开始并持续3天的延迟选择性头部冷却可能有可能显著改善中度至重度缺氧缺血性脑病的结局。
Objective. Cerebral hypothermia has been shown to reduce damage from experimental hypoxia-ischemia if started shortly after reperfusion. However, in the newborn infant it may not be feasible to determine prognosis so soon after exposure to asphyxia. The aim of this study was to determine whether head cooling, delayed until shortly before the onset of postasphyxial seizure activity, is neuroprotective.Methods. Unanesthetized near-term fetal sheep in utero were subjected to 30 minutes of cerebral ischemia. Later, at 5.5 hours, they were randomized to either cooling (n = 7) or sham cooling (n = 10) for 72 hours. Intrauterine cooling was induced by circulating cold water through a coil around the fetal head. The water temperature was titrated to reduce fetal extradural temperature from 39.1 +/- 0.1 degrees C to between 30 degrees C and 33 degrees C, while maintaining esophageal temperature >37 degrees C.Results. Cerebral cooling suppressed the secondary rise in cortical impedance (a measure of cytotoxic edema), but did not prevent delayed seizures, 8 to 30 hours after ischemia. Transient metabolic changes including increased plasma lactate and glucose levels were seen with a moderate sustained rise in blood pressure. This severe cerebral insult resulted in depressed residual parietal electroencephalographic activity after 5 days recovery (-14.2 +/- 1.5 decibels), associated with a watershed distribution of neuronal loss leg, 94 +/- 4% in parasagittal cortex and 77 +/- 4% in the lateral cortex). Hypothermia was associated with better recovery of electroencephalographic activity (-8.9% +/- 1.8 decibels) and substantially reduced neuronal loss in the parasagittal cortex (46 +/- 13%), the lateral cortex (9 +/- 4%), and other regions except the cornu ammonis sectors 1 and 2 of the hippocampus.Conclusions. Delayed selective head cooling begun before the onset of postischemic seizures and continued for 3 days may have potential to significantly improve the outcome of moderate to severe hypoxic-ischemic encephalopathy.