The Apoptotic and Inflammatory Response of Brain Striatal Tissue to Extracorporeal Membrane Oxygenation (ECMO) Following the Model of Cardiac Arrest in Young Piglets

We investigated the effects of ECMO on pro-apoptotic and pro-inflammatory signaling in the striatum of piglets following cardiac arrest. 3-week-old piglets were anesthetized, paralyzed and ventilated. Oxygen in the ventilated gas was decreased from 21% to 7% - 10% over 30 min, then ventilation stopped until cardiac arrest. Three minutes after arrest, resuscitation began in two groups, without ECMO (CA) and with ECMO (ECMO). In a control group (C), the animals were sham operated. After 6 hours of recovery, the piglets were euthanized and stratum harvested. Measurement of apoptotic and inflammatory proteins was performed by RayBiotech, Inc. The results are means (6) ± SEM. There were no differences between CA and ECMO groups for anti-apoptotic proteins. ECMO significantly decreased pro-apoptotic proteins (Bax, cytoC, IGFBP-6, TNF-beta and TRAIR 1 and 3) as compared to CA group. Bcl-2 to Bax ratio increased in ECMO group suggesting that ECMO can least partially protect striatum from apoptotic injury. With respect to inflammation, ECMO significantly decreased both anti-inflammatory (ANG-1, FGF-21, IFN-alpha and beta, IGF-2, IL-10, IL-13, IL-1ra, IL-22, IL-4, IL-6, NCAM-1, SCF, TGF-alpha, TIMP-1and 2, VECF) and pro-inflammatory proteins (IL-12p40, IL-21, IL-15, IL-1 alpha and beta, IL-8, MIP-1 beta, OPG, PIGF-2, RANTES and TGF beta) in striatum of piglets. Conclusions: In a piglet model of cardiac arrest, ECMO significantly reduced levels of pro-apoptotic proteins without changing the levels of anti-apoptotic proteins. ECMO also significantly decreased the levels of both pro- and anti-inflammatory proteins. This decrease in the levels of both pro- and anti-inflammatory proteins may lead to disturbed neuronal metabolism and amplify inflammatory cell death.

Granulocyte-colony stimulating factor suppresses early inflammatory response of striatum in a cardiopulmonary bypass-circulatory arrest model of ischemic brain injury in newborn piglets

We investigated the effect of Granulocyte-Colony Stimulating Factor (G-CSF) on expression of pro- and anti-inflammatory proteins in the striatum of new- born 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.