We investigated the effect of Granulocyte-Colony Stimulating Factor (G-CSF) on expression of pro-and anti-inflammatory proteins in the striatum of newborn piglet brain following cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Piglets were placed on CPB, cooled to 18˚C, subjected to 30 min of DHCA and 1 h of low-flow (20 ml/kg/min), rewarmed to 37˚C, separated from CPB circuit and monitored for 2 h. Striatum was then isolated for protein analysis. The levels of proteins are presented relative to the mean in the control group (mean ± SEM, n = 6). DHCA increased the levels of pro-inflammatory proteins: IL-1alpha (158% 23%, P = 0.05), IL-6 (152% 16%, P = 0.03), TNF-alpha (144% 2%, P = 0.003), MIP-3 alpha (148% 12.6%, P = 0.03), NAP-3 (216% 16%, P = 0.05), GRO (165% 19%, P = 0.03) and BLC (140.4 15%, P = 0.05). Compared to DHCA, the G-CSF-treated group had significantly decreased levels of IL-6 (110.8% 11% vs. 152% 16%, P = 0.05), TNF-alpha (120.6% 5.4% vs. 144% 2%, P = 0.001), MIP-3 alpha (148% 12.6% vs. 104.8% 13%, P = 0.02) and NAP-2 (216% 16% vs. 122% 23%, P = 0.002). The levels of anti-inflammatory proteins did not change in DHCA group compared to control, except for VEGF which decreased to 37.5% 9%, P = 0.003. The levels of all protective proteins in the G-CSF group increased versus the DHCA group, but the increases did not attain a P value of 0.05. Conclusions: In an immature brain subjected to circulatory arrest, the early inflammatory response in the striatum is diminished by pretreatment with G-CSF.