Abstract WP116: Early Hypothermia, But Not Delayed Hypothermia Ameliorates Ischemic Stroke Through Anti-inflammatory Process
Hypothermia is neuroprotective against many acute neurological insults. We and others have previously shown that protection by hypothermia is associated with the suppression of the inflammatory response that accompanies stroke. However, comparative mechanisms of the anti-inflammatory process through different hypothermic paradigms have surprisingly not been studied. In this study, we treated mice to early (protective) and delayed (not protective) hypothermia in a stroke model and compared the effect of cooling on the inflammatory response. We also explored the influence of a novel protein, triggering receptor expressed on myeloid cells-2 (TREM2), which is thought to be an important receptor involved in the innate immune response. TREM2 has previously been shown to promote phagocytosis of apoptotic neurons. We subjected male C57/BL6 mice to permanent middle cerebral artery occlusion (MCAO). We identified 2 cooling paradigms, one where cooling (rectal temp=30C) began at the onset of MCAO (early) and a second where cooling began 1h later (delayed). In both cases, cooling was maintained for 2h. A 3rd group was maintained at normothermia as a control (36C). Mice were survived 1, 3, 7, 14 & 30d (n=6/group/time point). Mice from the normothermic and delayed cooling groups had similar ischemic lesions sizes and neurological performance, but mice cooled early showed marked protection as evidenced by smaller lesion size and few neurological deficits at all time points (p < 0.05, 40% reduction). Microglia/macrophages and TREM2 were decreased only in the early cooling group (P < 0.05). Immune cells were reduced only where hypothermia was protective and we conclude that inflammation is probably related to the amount of injury present, and not whether cooling occurred.
- © 2012 by American Heart Association, Inc.