Abstract 178: Regional and Temporal Brain Tissue Cytokine Profile After Prolonged Hypothermic Cardiac Arrest in Rats: A Novel Role for Striatum
Background: Prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation. Microglia are a major source of cytokines. We previously showed that microglial proliferation is attenuated by deep hypothermia or intrahippocampal injection of clodronate, without affecting extensive neuronal death in the hippocampus. In this study, we investigated the temporal profile of brain tissue cytokine production after moderate or deep intra-CA hypothermia, with or without pretreatment with clodronate to deplete microglia. We hypothesized that 1) cytokine production would be decreased with deeper hypothermia; 2) intrahippocampal injection of clodronate would decrease cytokine levels in hippocampus after CA in rats.
Methods: 24 h after injection of clodronate or saline into right or left hippocampus, rats were subjected to 20 min CA at different levels of hypothermia induced by ice-cold (IC) or room-temperature (RT) aortic flush. After resuscitation with cardiopulmonary bypass, rats were sacrificed at 6 h (n=12) or 24 h (n=11). Brain cytokines were analyzed in cortex, striatum, hippocampus and cerebellum in each hemisphere.
Results: Intra-CA temperature was lower after IC vs. RT flush (21°C vs 30°C, p<0.05). CA resulted in significant temperature-, region-and temporal-dependent differences in brain cytokines. Globally, IL-10 was higher in IC vs. RT at 6 h (p=0.002), while IL-1α and IL-2 trended to lower levels (IC vs RT, p=0.099 for both). Striatum showed a massive release of IL-1α and TNFα (10-and 16-fold higher than in hippocampus). In contrast, IL-12 was 50-fold higher in hippocampus vs. striatum. In striatum, IL-1α was lower in IC vs RT group (p<0.001). Clodronate decreased only IL-12 in hippocampus (p<0.05). At 24 h, a more global cytokine response was seen across brain regions. In hippocampus, IL-1α levels increased 4-fold, while TNFα levels decreased 60-fold.
Discussion: We report important regional and temporal differences in the brain cytokine response to hypothermic CA, with a previously unreported unique role of striatum. Hypothermia showed protective effects, while clodronate showed only a local effect in hippocampus.
- © 2010 by American Heart Association, Inc.