Granulocyte colony stimulating factor reduces brain injury in a cardiopulmonary bypass-circulatory arrest model of ischemia in a newborn piglet.

Document Type

Article

Publication Date

11-2014

Identifier

DOI: 10.1007/s11064-014-1399-7; PMCID: PMC4265391

Abstract

Ischemic brain injury continues to be of major concern in patients undergoing cardiopulmonary bypass (CPB) surgery for congenital heart disease. Striatum and hippocampus are particularly vulnerable to injury during these processes. Our hypothesis is that the neuronal injury resulting from CPB and the associated circulatory arrest can be at least partly ameliorated by pre-treatment with granulocyte colony stimulating factor (G-CSF). Fourteen male newborn piglets were assigned to three groups: deep hypothermic circulatory arrest (DHCA), DHCA with G-CSF, and sham-operated. The first two groups were placed on CPB, cooled to 18 °C, subjected to 60 min of DHCA, re-warmed and recovered for 8-9 h. At the end of experiment, the brains were perfused, fixed and cut into 10 µm transverse sections. Apoptotic cells were visualized by in situ DNA fragmentation assay (TUNEL), with the density of injured cells expressed as a mean number ± SD per mm(2). The number of injured cells in the striatum and CA1 and CA3 regions of the hippocampus increased significantly following DHCA. In the striatum, the increase was from 0.46 ± 0.37 to 3.67 ± 1.57 (p = 0.002); in the CA1, from 0.11 ± 0.19 to 5.16 ± 1.57 (p = 0.001), and in the CA3, from 0.28 ± 0.25 to 2.98 ± 1.82 (p = 0.040). Injection of G-CSF prior to bypass significantly reduced the number of injured cells in the striatum and CA1 region, by 51 and 37 %, respectively. In the CA3 region, injured cell density did not differ between the G-CSF and control group. In a model of hypoxic brain insult associated with CPB, G-CSF significantly reduces neuronal injury in brain regions important for cognitive functions, suggesting it can significantly improve neurological outcomes from procedures requiring DHCA.

Journal Title

Neurochemical research

Volume

39

Issue

11

First Page

2085

Last Page

2092

MeSH Keywords

Animals; Animals, Newborn; Brain; Brain Injuries; Cardiopulmonary Bypass; Circulatory Arrest, Deep Hypothermia Induced; Disease Models, Animal; Granulocyte Colony-Stimulating Factor; Hypothermia, Induced; Ischemia; Male; Swine

Keywords

Brain Injuries; Cardiopulmonary Bypass; Deep Hypothermia Induced Circulatory Arrest; Disease Models, Animal; Granulocyte Colony-Stimulating Factor; Induced Hypothermia; Ischemia; Swine

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