Early Response of Inflammatory Proteins in the Striatum and Hippocampus of Newborn Piglets Following Cardiopulmonary Bypass and Circulatory Arrest

Abstract

Background and aims: Inflammation plays a key role in ischemic brain injury. We examined the levels of select inflammatory proteins in the striatum and hippocampus of newborn piglets in a cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) ischemia model. Methods: Piglets were placed on CPB, cooled to 18°C, subjected to 30min of DHCA and 1hr of low-flow (20ml/kg/min), rewarmed to 37°C, separated from CPB, monitored for 2hrs and then striatum and hippocampus were isolated for protein analysis. Protein levels are presented in arbitrary units (mean±SE). Results: Striatum: CPB/DHCA increased, as compared with sham operated animals, pro-inflammatory cytokines implicated in ischemic brain injury: interleukin 1 (365±12.7 vs 583±83, p< 0.047) and tumor necrosis factor-alpha (318±37 vs 402±18, p< 0.05); chemotactic cytokines: growth regulated protein (GRO) (226±16 vs 376±42, p< 0.02), GRO-alpha (178±16 vs 297±17, p< 0.001) and interleukin-8 (591±47 vs 728±40, p< 0.05); chemokines: macrophage inflammatory protein-3 (58±8 vs 88±7, p< 0.05) and eotaxin (107±7 vs 164±17, p< 0.02). Vascular endothelial growth factor, potentially protective, was decreased (25±5 vs 11±3, p< 0.05). Hippocampus: There were no significant differences in the above proteins after CBP/DHCA. However, potentially protective proteins, interleukin-10 (338±18 vs 405±5, p< 0.02) and transforming growth factor beta (389±24 vs 460±16, p< 0.05), were increased. Conclusions: In piglet model of CBP/DHCA, early response of proteins regulating inflammation in the brain is region-dependent: proteins exacerbating ischemic injury are increased in the striatum, whereas those with potential protective role are increased in the hippocampus.