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 degrees 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 degrees C) forebrain ischemia by two-vessel 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 micrograms) 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 < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic neuronal damage after transient global ischemia. In postinjury settings where restricted durations of mild hypothermia can be induced, anti-inflammatory treatments, including IL-10, may promote chronic neuroprotection.
Department of Neurology, The Miami Project to Cure Paralysis, Miami, Florida, 33101, USA. ddietric@miamiproj.med.miami.edu
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Dietrich
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Busto
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Bethea
D000818:Animals; D001794:Blood Pressure; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D007036:Hypothermia, Induced; D016753:Interleukin-10 / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018696:Neuroprotective Agents; D016753:Interleukin-10