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 interventions may delay rather than provide long-lasting neuroprotection. The purpose of this study was to determine whether mild hypothermia (33–34°C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) would protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37°C) forebrain ischemia by two-vessel occlusion followed immediately by: (a) 4 h of normothermic (37°C) reperfusion (n=5); (b) 4 h of postischemic hypothermia (33–34°C) (n=5); (c) 4 h of normothermia plus IL-10 (5 μg) treatment 30 min after ischemia and at 3 days (n=5); or (d) 4 h of hypothermia plus IL-10 treatment (n=5). Rats survived for 2 months and were perfusion fixed for quantitative histopathological assessment of CA1 hippocampus. Postischemic normothermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatment of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P