School of Clinical Sciences, University of Bristol, St Michael's Hospital, Bristol, BS28EG, United Kingdom.
Stroke. 2012 Dec;43(12):3364-70. doi: 10.1161/STROKEAHA.112.674481. Epub 2012 Sep 20.
Hypothermia (HT) for neonatal hypoxic-ischemic encephalopathy is advised to start within the first 6 hours after birth. There is some clinical evidence that HT is more effective against moderate than against severe hypoxic-ischemic encephalopathy, but it is unknown whether delayed HT beyond 6 hours is effective or even injurious.
One-hundred seven 7-day-old rat pups underwent unilateral hypoxia-ischemia of moderate severity. Pups were randomized to receive 5 hours of normothermia (NT) or HT starting immediately, 3 hours, 6 hours, or 12 hours after the 90-minute hypoxic period. One-hundred five 7-day-old rat pups underwent severe hypoxia-ischemia lasting 150 minutes, followed by the same group design as mentioned. Relative area loss of the left/right hemisphere was measured after 1 week of survival.
In the moderate NT group, the mean area loss of the left hemisphere was 40.5%. The area loss was significantly decreased to 24.8% with immediate HT (P<0.05) and increased linearly with the delay of HT by 1.788% per hour until at least 6 hours of delay (linear regression, P=0.026). After 12-hour delayed HT, the area loss was similar to the moderate NT group (41.1%). After severe NT, the mean area loss of the left hemisphere was 59.3%. Immediate HT, 3-hour delayed HT, and 6-hour delayed HT all resulted in similar area loss, whereas the 12-hour delayed-HT resulted in significantly increased area loss (69.5%; P=0.032).
Immediate and delayed (≤6 hours) HT provides neuroprotection after moderate hypoxia-ischemia in neonatal rats. This neuroprotection decreases linearly with increasing delay. After severe insults, however, immediate or delayed HT≤6 hours provides no neuroprotection. Twelve-hour delayed hypothermia increased brain injury after severe hypoxia-ischemia, which is of clinical concern.
对于患有缺氧缺血性脑病的新生儿，建议在出生后 6 小时内开始进行低温治疗（HT）。有一些临床证据表明，HT 对中度缺氧缺血性脑病的疗效比对重度缺氧缺血性脑病更有效，但尚不清楚 6 小时后延迟 HT 是否有效，甚至是否有害。
107 只 7 天大的大鼠幼崽接受了单侧中重度缺氧缺血。幼崽随机接受 5 小时的常温治疗（NT）或 HT，HT 开始于缺氧期 90 分钟后立即、3 小时、6 小时或 12 小时。105 只 7 天大的大鼠幼崽接受了持续 150 分钟的重度缺氧缺血，然后采用相同的分组设计。存活 1 周后测量左侧/右侧大脑半球的相对面积损失。
在中度 NT 组中，左侧大脑半球的平均面积损失为 40.5%。立即进行 HT 可显著降低面积损失，降至 24.8%（P<0.05），并且 HT 延迟 1 小时，面积损失线性增加 1.788%，直至至少 6 小时的延迟（线性回归，P=0.026）。12 小时延迟 HT 后，面积损失与中度 NT 组相似（41.1%）。在重度 NT 后，左侧大脑半球的平均面积损失为 59.3%。立即 HT、3 小时延迟 HT 和 6 小时延迟 HT 均导致相似的面积损失，而 12 小时延迟 HT 导致明显增加的面积损失（69.5%；P=0.032）。
在新生大鼠中度缺氧缺血后，立即和延迟（≤6 小时）HT 提供神经保护。这种神经保护作用随延迟时间的增加呈线性下降。然而，在严重损伤后，立即或延迟≤6 小时的 HT 不能提供神经保护。12 小时延迟性低温治疗会增加严重缺氧缺血后的脑损伤，这是临床上需要关注的问题。
