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Granulocyte Colony Stimulating Factor Reduces Brain Injury in a Cardiopulmonary Bypass-Circulatory Arrest Model of Ischemia in a Newborn Piglet

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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 mm2. 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.

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Acknowledgments

The research was supported by a Grant HL-58669 from the National Institutes of Health, Bethesda, MD, USA.

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Authors and Affiliations

  1. Section of Cardiac Surgery, The Ward Family Heart Center, Children’s Mercy Hospital and Clinics, 2401 Gillham Road, Kansas City, MO, 64108, USA

    Peter Pastuszko

  2. Department of Anesthesiology, Mayo Clinic, Rochester, MN, USA

    Gregory J. Schears

  3. Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    William J. Greeley

  4. Department of Biochemistry and Biophysics, School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Joanna Kubin, David F. Wilson & Anna Pastuszko

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  1. Peter Pastuszko
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  2. Gregory J. Schears
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Correspondence to Peter Pastuszko.

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Pastuszko, P., Schears, G.J., Greeley, W.J. et al. Granulocyte Colony Stimulating Factor Reduces Brain Injury in a Cardiopulmonary Bypass-Circulatory Arrest Model of Ischemia in a Newborn Piglet. Neurochem Res 39, 2085–2092 (2014). https://doi.org/10.1007/s11064-014-1399-7

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