METHODS: Various regimens of z-VAD, z-DEVD, and control
DMSO were given to rats subjected to either 4-vessel occlusion
ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal
middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global
ischemia, treatments were given immediately after
ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal
ischemia experiments were done. Injection times were 60 minutes into
ischemia (experiment 1) and 60 minutes into
ischemia plus 30 and 120 minutes after
ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during
ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after
ischemia with telemetry probes. Because
hyperthermia accompanied z-DEVD treatment, an extra z-DEVD-treated group (MCAo) was included with temperature clamped at normothermia.
RESULTS: Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global
ischemia. In focal
ischemia, both drugs significantly reduced
infarction, but only in the third experiment, and the prevention of
hyperthermia that accompanied z-DEVD treatment did not alter this.
CONCLUSIONS: