The effect of cerebral hypothermia on white and grey matter injury induced by severe hypoxia in preterm fetal sheep
The effect of cerebral hypothermia on white and grey matter injury induced by severe hypoxia in preterm fetal sheep
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DOI：
10.1113/jphysiol.2006.119602
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发表时间：
2007-01-15
影响因子：
5.5
通讯作者：
Gunn, A. J.
中科院分区：
文献类型：
--
作者：
Bennet, L.;Roelfsema, V.;Gunn, A. J.
实验性缺氧缺血后，长期中度脑低温持续具有神经保护作用;然而，尚未在早产儿脑中进行测试。早产（0.7妊娠）胎羊接受完全脐带闭塞25分钟，然后在闭塞或假冷却结束后90分钟至70小时进行脑低温（胎羊硬膜外温度从39.4 +/- 0.3降至29.5 +/- 2.6 ℃）。闭塞导致严重酸中毒和严重低血压，在闭塞解除后迅速恢复。恢复3天后，脑电频谱频率，但不是总强度，增加在低血压闭塞组与常温闭塞。低温与脑室周围白色物质中未成熟少突胶质细胞的损失显著总体减少（P < 0.001），以及海马和基底节中神经元的损失（P < 0.001）相关，并抑制了激活的半胱天冬酶3和小胶质细胞（isolectin-B4阳性）。阻断后脑室周围白色物质的增殖明显减少（P < 0.05），而低温后无明显改善。总之，早产儿在深度缺氧损伤后延迟、延长的头部冷却与神经元和未成熟少突胶质细胞损失的显著减少相关，3天恢复后EEG和血液动力学改善的证据相关，但也与脑室周围区域细胞增殖的持续减少相关。需要进一步的研究来评估冷却对大脑生长和成熟的长期影响。
Prolonged, moderate cerebral hypothermia is consistently neuroprotective after experimental hypoxia-ischaemia; however, it has not been tested in the preterm brain. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4 +/- 0.3 to 29.5 +/- 2.6 degrees C) from 90 min to 70 h after the end of occlusion or sham cooling. Occlusion led to severe acidosis and profound hypotension, which recovered rapidly after release of occlusion. After 3 days recovery the EEG spectral frequency, but not total intensity, was increased in the hypothermia-occlusion group compared with normothermia-occlusion. Hypothermia was associated with a significant overall reduction in loss of immature oligodendrocytes in the periventricular white matter (P < 0.001), and neuronal loss in the hippocampus and basal ganglia (P < 0.001), with suppression of activated caspase-3 and microglia (isolectin-B4 positive). Proliferation was significantly reduced in periventricular white matter after occlusion (P < 0.05), but not improved after hypothermia. In conclusion, delayed, prolonged head cooling after a profound hypoxic insult in the preterm fetus was associated with a significant reduction in loss of neurons and immature oligodendroglia, with evidence of EEG and haemodynamic improvement after 3 days recovery, but also with a persisting reduction in proliferation of cells in the periventricular region. Further studies are required to evaluate the long-term impact of cooling on brain growth and maturation.