Torregrosa G, Barberá M D, Ortí M, Centeno J M, Salom J B, Justicia C, Planas A M, Alborch E
Centro de Investigación, Hospital Universitario La Fe, Valencia, Spain.
Hippocampus. 2001;11(2):146-56. doi: 10.1002/hipo.1032.
The role of gene induction (expression of HSP72 and c-JUN proteins) and delayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischemia. The animals were subjected to 20-min ischemia (bilateral occlusion of the external carotid arteries plus bilateral jugular vein compression) and allowed to reperfuse for 2 h, and then 1, 3, and 7 days. Histological signs of cell loss were not found in the hippocampus at 2 h, 1 day, or 3 days of reperfusion. However, such an ischemic insult produced extensive, selective, and delayed degeneration in the hippocampus, as 68% of the neurons in CA1 had died at 7 days, but cell loss was not detected in CA3 and dentate gyrus fields. Concomitantly, a high percentage of TUNEL-positive CA1 neurons (60+/-9%, mean +/- SEM) was seen at 7 days, but not at the earlier time points. Mild induction of HSP72 was detected in the goat hippocampus after ischemia. The maximum percentage of HSP72-positive neurons (10-15%) was shown at 3 days of reperfusion and was concentrated mainly in the CA3 field, subiculum, and hilus, rather than in the CA1 field, whereas HSP72 expression was hardly detected at 7 days. At this later time point, scattered induction of nuclear c-JUN was found in a few neurons. The results show that: 1) postischemic delayed neuronal death selectively affects the CA1 field in the goat hippocampus, a phenomenon which seems to take longer to develop than in previously reported rodent models; and 2) postischemic expression of c-JUN does not appear to be related to cell death or survival, while the inability of most CA1 neurons to express HSP72 could contribute to neuronal death.
在山羊全脑短暂缺血后，研究了基因诱导（热休克蛋白72（HSP72）和c-JUN蛋白的表达）和延迟性缺血性细胞死亡（DNA片段原位标记）在山羊海马体中的作用。对动物进行20分钟的缺血处理（双侧颈外动脉闭塞加双侧颈静脉压迫），然后再灌注2小时，之后分别在1天、3天和7天进行观察。在再灌注2小时、1天或3天时，海马体中未发现细胞丢失的组织学迹象。然而，这种缺血性损伤在海马体中导致了广泛、选择性和延迟性的变性，因为在7天时，CA1区68%的神经元已经死亡，但在CA3区和齿状回区域未检测到细胞丢失。与此同时，在7天时可见高比例的TUNEL阳性CA1神经元（60±9%，平均值±标准误），但在早期时间点未出现。缺血后在山羊海马体中检测到HSP72的轻度诱导。HSP72阳性神经元的最大比例（10 - 15%）出现在再灌注3天时，主要集中在CA3区、海马下脚和齿状回，而不是CA1区，而在7天时几乎检测不到HSP72的表达。在这个较晚的时间点，在少数神经元中发现了核c-JUN的散在诱导。结果表明：1）缺血后延迟性神经元死亡选择性地影响山羊海马体中的CA1区，这种现象的发展似乎比先前报道的啮齿动物模型要慢；2）缺血后c-JUN的表达似乎与细胞死亡或存活无关，而大多数CA1神经元无法表达HSP72可能导致神经元死亡。
