The Effect of Postischemic Hypothermia on Apoptotic Cell Death in the Neonatal Rat Brain
The Effect of Postischemic Hypothermia on Apoptotic Cell Death in the Neonatal Rat Brain
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DOI：
10.1159/000329924
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发表时间：
2011-01-01
影响因子：
2.9
通讯作者：
Yager, Jerome Y.
中科院分区：
文献类型：
--
作者：
Askalan, Rand;Wang, Carol;Yager, Jerome Y.
背景与目的：亚低温是目前对发育期脑缺血性损伤最有效的神经保护治疗方法。然而，低温神经保护的机制尚不清楚。我们试图研究低温是否通过调节缺血诱导的细胞凋亡来介导神经保护作用。方法：7日龄大鼠随机分为对照组和缺氧缺血（HI）组。HI组结扎颈内动脉并切断。随后在8%氧气下短暂缺氧90 min。在对照组大鼠中，分离颈内动脉，但不结扎。缺氧事件后，立即将HI组中的幼仔置于维持在28摄氏度的水浴中24小时（核心温度为31摄氏度），或者将其保持在正常温度的环境中。在HI损伤后24、48和72小时以及1周处死动物。处理脑切片进行免疫组织化学和Western印迹。结果：常温下，梗死中心区Caspase 3的表达在各时间点均显著高于梗死周边区。低温降低了核心区caspase 3的表达，但对梗死周围区的影响不大。低温可减少凋亡诱导因子向核心区和梗死周围区细胞核的移位。与此同时，X-连锁的凋亡抑制因子（XIAP）的表达显着增强，在低温缺血的核心，但不是在周围梗死区。结论：低温对caspase依赖性细胞凋亡的调节可能是通过上调XIAP介导的。然而，低温对caspase非依赖性凋亡的影响可能是通过XIAP非依赖性机制介导的。重要的是，这些作用在缺血性病变的核心和半影区域中介导。版权所有（C）2011 S. Karger AG，巴塞尔
Background and Objective: Hypothermia is the most effective neuroprotective therapy against ischemic injury in the developing brain. However, the mechanism of hypothermic neuroprotection is not well understood. We sought to investigate whether hypothermia mediates neuroprotection by modulating ischemia-induced apoptosis. Methods: Seven-day-old rat pups were randomly assigned to either control or hypoxia-ischemia (HI) groups. In the HI group, the internal carotid artery was ligated and cut. This was followed by transient hypoxia at 8% oxygen for 90 min. In the control rats, the internal carotid was isolated but not ligated. Immediately after the hypoxic episode, pups in the HI group were either placed in water baths maintained at 28 degrees C for 24 h (core temperatures at 31 degrees C) or they remained in a normothermic environment. Animals were sacrificed at 24, 48 and 72 h and 1 week after the HI insult. Brain sections were processed for immunohistochemistry and Western blots. Results: Caspase 3 expression was significantly higher in the core compared with the peri-infarct area at all time points in normothermic rats. Hypothermia reduced caspase 3 expression in the core but had little effect in the peri-infarct area. Hypothermia reduced apoptosis-inducing factor translocation to the nucleus in the core and peri-infarct area. Concurrently, X-linked inhibitor of apoptosis (XIAP) expression was significantly potentiated in the hypothermic-ischemic core but not in the peri-infarct area. Conclusion: Hypothermic modulation of caspase-dependent apoptosis may be mediated by upregulating XIAP. However, the effect of hypothermia on caspase-independent apoptosis may be mediated by XIAP-independent mechanisms. Importantly, these effects are mediated in both the core and the penumbral regions of ischemic lesion. Copyright (C) 2011 S. Karger AG, Basel