INTRAISCHEMIC BUT NOT POSTISCHEMIC BRAIN HYPOTHERMIA PROTECTS CHRONICALLY FOLLOWING GLOBAL FOREBRAIN ISCHEMIA IN RATS
INTRAISCHEMIC BUT NOT POSTISCHEMIC BRAIN HYPOTHERMIA PROTECTS CHRONICALLY FOLLOWING GLOBAL FOREBRAIN ISCHEMIA IN RATS
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DOI：
10.1038/jcbfm.1993.71
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发表时间：
1993-07-01
影响因子：
6.3
通讯作者：
GINSBERG, MD
中科院分区：
文献类型：
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作者：
DIETRICH, WD;BUSTO, R;GINSBERG, MD
我们研究了全前脑缺血后脑低温（30 ℃）是否会永久保护海马。在麻醉大鼠中，通过双侧颈动脉阻断加低血压（50 mm Hg）来产生全脑缺血。在缺血后低温组中，脑温在10 min缺血损伤期间维持在37 ℃，但从再循环期开始3 min降至30 ℃，并在30 ℃下维持3 h。在正常体温的动物中，缺血内和缺血后的大脑温度保持在37 ℃。恢复3天、7天或2个月后，定量CA 1海马组织学损伤的程度。在缺血后3天，缺血后低温显着保护海马CA 1区相比，常温动物。例如，在内侧、中间和外侧CA 1亚区，缺血后低温使正常神经元的数量增加了20、13和9倍（p < 0.01）。然而，在缺血损伤后7天，缺血后低温保护的程度显著降低。在这种情况下，正常神经元的数量平均只增加了常温下的三倍。超微结构分析7天postischimic低温大鼠表现出不同程度的损伤CA 1锥体神经元周围的反应性星形胶质细胞和小胶质细胞。在缺血损伤后2个月，没有表现出保护的趋势。与缺血后低温相比，在缺血内低温后2个月观察到显著的保护作用。这些数据表明，缺血内，而不是缺血后，脑低温提供了慢性保护短暂脑缺血后的海马。缺血后低温不能在3天后长期保护可能表明（a）缺血后低温仅仅延迟缺血性细胞死亡和/或（B）缺血后脑经历二次损伤。在缺血后治疗方案中，需要进行长期生存研究以准确确定全脑缺血后的最终组织病理学结果。
We investigated whether postischemic brain hypothermia (30-degrees-C) would permanently protect the hippocampus following global forebrain ischemia. Global ischemia was produced in anesthetized rats by bilateral carotid artery occlusion plus hypotension (50 mm Hg). In the postischemic hypothermic group, brain temperature was maintained at 37-degrees-C during the 10-min ischemic insult but reduced to 30-degrees-C starting 3 min into the recirculation period and maintained at 30-degrees-C for 3 h. In normothermic animals, intra- and postischemic brain temperature was maintained at 37-degrees-C. After recovery for 3 days, 7 days, or 2 months, the extent of CA1 hippocampal histologic injury was quantitated. At 3 days after ischemia, postischemic hypothermia significantly protected the hippocampal CA1 sector compared with normothermic animals. For example, within the medial, middle, and lateral CA1 subsectors, the numbers of normal neurons were increased 20-, 13-, and 9-fold by postischemic hypothermia (p < 0.01). At 7 days after the ischemic insult, however, the degree of postischemic hypothermic protection was significantly reduced. In this case, the numbers of normal neurons were increased an average of only threefold compared with normothermia. Ultrastructural analysis of 7-day postischemic hypothermic rats demonstrated CA1 pyramidal neurons showing variable degrees of injury surrounded by reactive astrocytes and microglial cells. At 2 months after the ischemic insult, no trend for protection was demonstrated. In contrast to postischemic hypothermia, significant protection was seen at 2 months following intraischemic hypothermia. These data indicate that intraischemic, but not postischemic, brain hypothermia provides chronic protection to the hippocampus after transient brain ischemia. The inability of postischemic hypothermia to protect chronically after 3 days could indicate that (a) postischemic hypothermia merely delays ischemic cell death and/or (b) the postischemic brain undergoes a secondary insult. In postischemic treatment protocols, chronic survival studies are required to determine accurately the ultimate histopathological outcome following global cerebral ischemia.