Temporospatial expression of HSP72 and c-JUN, and DNA fragmentation in goat hippocampus after global cerebral ischemia

The role of gene induction (expression of HSP72 and c-JUN proteins) and del ayed ischemic cell death (in situ labeling of DNA fragmentation) have been investigated in the goat hippocampus after transient global cerebral ischem ia. The animals were subjected to 20-min ischemia (bilateral occlusion of t he external carotid arteries plus bilateral jugular vein compression) and a llowed 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 gyru s fields. Concomitantly, a high percentage of TUNEL-positive CA1 neurons (6 0 +/- 9%, mean +/- SEM) was seen at 7 days, but not at the earlier time poi nts. Mild induction of HSP72 was detected in the goat hippocampus after isc hemia. The maximum percentage of HSP72-positive neurons (10-15%) was shown at 3 days of reperfusion and was concentrated mainly in the CA3 field, subi culum, and hilus, rather than in the CA1 field, whereas HSP72 expression wa s 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) post ischemic delayed neuronal death selectively affects the CA1 field in the go at 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 inabilit y of most CA1 neurons to express HSP72 could contribute to neuronal death. Hippocampus 2001;11:146-156. (C) 2001 Wiley-Liss, Inc.