Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats

Experimental studies have demonstrated that postischemic therapeutic interv entions may delay rather than provide long-lasting neuroprotection. The pur pose of this study was to determine whether mild hypothermia (33-34 degrees C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) wou ld protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37 degrees C) forebrain ischemia by two-vesse l occlusion followed immediately by: (a) 4 h of normothermic (37 degrees C) reperfusion (n = 5); (b) 4 h of postischemic hypothermia (33-34 degrees C) (n = 5); (c) 4 h of normothermia plus IL-10 (5 mu g) treatment 30 min afte r ischemia and at 3 days (n = 5); or (d) 4 h of hypothermia plus IL-10 trea tment (n = 5). Rats survived for 2 months and were perfusion fixed for quan titative histopathological assessment of CA1 hippocampus. Postischemic norm othermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatmen t of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic n euronal damage after transient global ischemia. In postinjury settings wher e restricted durations of mild hypothermia can be induced, anti-inflammator y treatments, including IL-10, may promote chronic neuroprotection. (C) 199 9 Academic Press.