Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep.
Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep.
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DOI：
10.1038/srep25178
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发表时间：
2016-04-28
影响因子：
4.6
通讯作者：
Gunn AJ
中科院分区：
文献类型：
--
作者：
Davidson JO;Yuill CA;Zhang FG;Wassink G;Bennet L;Gunn AJ
现代新生儿护理的一个主要挑战是进一步改善缺氧缺血性脑病低温治疗后的结局。在这项研究中，我们测试了延长冷却时间是否可以减少白色物质的损害。足月胎羊（0.85妊娠）接受假缺血，然后是常温（n = 8）或双侧颈动脉闭塞30分钟，然后是3天的常温（n = 8），3天的低温（n = 8）或5天的低温（n = 8）缺血后3小时开始。缺血后7天评估组织学。与假手术对照相比，缺血与髓鞘碱性蛋白（MBP）和Olig-2阳性少突胶质细胞的损失以及Iba-1阳性小胶质细胞的增加有关（p < 0.05）。与缺血-常温相比，3天和5天的低温与MBP和少突胶质细胞数量的相似的部分改善相关（p < 0.05）。与缺血-常温相比，两个低温组均具有减少的小胶质细胞活化（p < 0.05）。在缺血5天低温组，而不是缺血3天，小胶质细胞的数量仍然高于假手术对照组（p < 0.05）。总之，延迟性脑低温可部分保护胎羊全脑缺血后的白色物质。将冷却时间从3天延长到5天并没有进一步改善结果，可能与更多的残留小胶质细胞有关。
A major challenge in modern neonatal care is to further improve outcomes after therapeutic hypothermia for hypoxic ischemic encephalopathy. In this study we tested whether extending the duration of cooling might reduce white matter damage. Term-equivalent fetal sheep (0.85 gestation) received either sham ischemia followed by normothermia (n = 8) or 30 minutes of bilateral carotid artery occlusion followed by three days of normothermia (n = 8), three days of hypothermia (n = 8) or five days of hypothermia (n = 8) started three hours after ischemia. Histology was assessed 7 days after ischemia. Ischemia was associated with loss of myelin basic protein (MBP) and Olig-2 positive oligodendrocytes and increased Iba-1-positive microglia compared to sham controls (p < 0.05). Three days and five days of hypothermia were associated with a similar, partial improvement in MBP and numbers of oligodendrocytes compared to ischemia-normothermia (p < 0.05). Both hypothermia groups had reduced microglial activation compared to ischemia-normothermia (p < 0.05). In the ischemia-five-day hypothermia group, but not ischemia-three-day, numbers of microglia remained higher than in sham controls (p < 0.05). In conclusion, delayed cerebral hypothermia partially protected white matter after global cerebral ischemia in fetal sheep. Extending cooling from 3 to 5 days did not further improve outcomes, and may be associated with greater numbers of residual microglia.