TITLE:
Granulocyte-colony stimulating factor suppresses early inflammatory response of striatum in a cardiopulmonary bypass-circulatory arrest model of ischemic brain injury in newborn piglets
AUTHORS:
Peter Pastuszko, Gregory J. Schears, Joanna Kubin, William J. Greeley, Vinay Nadkarni, David F. Wilson, Anna Pastuszko
KEYWORDS:
Brain; Cardiopulmonary Bypass; Inflammatory Response; Animal Model
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.3 No.2,
April
25,
2013
ABSTRACT:
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.