Inhibition of Apoptosis Following Transient Forebrain Ischemia in Gerbils by Intraischemic Mild Hypothermia

ABSTRACT

BACKGROUND: A brief episode of global forebrain ischemia produces selective and often extensive neuronal loss in several vulnerable brain structures. This cell death does not occur immediately, but is delayed for hours to days. This process is termed delayed neuronal death (DND). Recently, several reports have suggested that an apoptotic process may be involved in DND. The most effective treatment at present is intraischemic hypothermia. Thus, we designed this study to investigate whether intraischemic mild hypothermia could inhibit apoptosis following transient forebrain ischemia in gerbils. METHODS: Twenty-four gerbils were divided into two groups based on intraischemic rectal temperature 34 degrees C(n=12) and 37 degrees C(n=12). Two additional gerbils underwent a sham operation. Cerebral ischemia was produced by occluding both carotid arteries for 10 minutes. The DNA fragmentation in the gerbil hippocapal CA1 area was determined by using the TUNEL method, and the results for the normothermic and the hypothermic groups were compared at 1, 3, and 7 days following 10-min transient ischemia (n=4 for each time point, respectively). RESULTS: 1. Percent dead hippocampal neurons were significantly decreased in the hypothermic group compared with the normothermic group at 1, 3, and 7 days following transient ischemia (p<0.05). 2. In the intraischemic normothermic group, TUNEL positive cells were first detected in the hippocampal CA1 at 3 days (1.9+/-0.6 cells/section), and the number was larger at 7 days following transient ischemia (127.8+/-16.3 cells/section). 3. In the intraischemic hypothermic group, no TUNEL positive cells were detected in the hippocampal CA1 at 1, 3, and 7 days following transient ischemia. CONCLUSION: The data suggest that delayed neuronal death following transient ischemia is, in part, apoptotic and that intraischemic mild hypothermia affords significant neuronal protection and prevents DNA fragmentation.