How long is sufficient for optimal neuroprotection with cerebral cooling after ischemia in fetal sheep?
How long is sufficient for optimal neuroprotection with cerebral cooling after ischemia in fetal sheep?
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DOI：
10.1177/0271678x17707671
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发表时间：
2018-06-01
影响因子：
6.3
通讯作者：
Gunn, Alistair J.
中科院分区：
文献类型：
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作者：
Davidson, Joanne O.;Draghi, Vittoria;Gunn, Alistair J.
轻度低温治疗新生儿缺氧缺血性脑病的最佳持续时间令人惊讶地不清楚。本研究评估了冷却48 h与72 h的相对有效性。胎羊（0.85胎龄）分别接受假缺血（n = 9）或30 min全脑缺血后常温（n = 8）或延迟低温（3 ~ 48 h（n = 8）或72 h（n = 8））。缺血与脑电图（EEG）功率、皮质和海马中的神经元、白色物质中的少突胶质细胞和髓鞘碱性蛋白表达以及Iba-1阳性小胶质细胞和增殖增加的严重损失相关。与正常体温相比，低温48小时与改善的结局相关，但与低温72小时相比，复温后EEG功率进行性恶化，神经元存活和髓鞘碱性蛋白受损，白色物质和皮质中有更多的小胶质细胞。这些结果表明，胎羊脑缺血后头部冷却48小时具有部分神经保护作用，但不如冷却72小时。48小时复温、随后EEG功率恶化和皮质炎症增加之间的密切关联强烈表明，过早复温可重新激活有害炎症。
The optimal duration of mild therapeutic hypothermia for neonates with hypoxic-ischemic encephalopathy is surprisingly unclear. This study assessed the relative efficacy of cooling for 48h versus 72h. Fetal sheep (0.85 gestation) received sham ischemia (n = 9) or 30min global cerebral ischemia followed by normothermia (n = 8) or delayed hypothermia from 3h to 48h (n = 8) or 72h (n = 8). Ischemia was associated with profound loss of electroencephalogram (EEG) power, neurons in the cortex and hippocampus, and oligodendrocytes and myelin basic protein expression in the white matter, with increased Iba-1-positive microglia and proliferation. Hypothermia for 48h was associated with improved outcomes compared to normothermia, but a progressive deterioration of EEG power after rewarming compared to 72h of hypothermia, with impaired neuronal survival and myelin basic protein, and more microglia in the white matter and cortex. These findings show that head cooling for 48h is partially neuroprotective, but is inferior to cooling for 72h after cerebral ischemia in fetal sheep. The close association between rewarming at 48h, subsequent deterioration in EEG power and increased cortical inflammation strongly suggests that deleterious inflammation can be reactivated by premature rewarming.