The Effect of Granulocyte Colony-Stimulating Factor on Expression of Selected Regulatory Proteins Responsible for Cell Injury or Survival in the Brain of Newborn Piglets Following Cardiopulmonary Bypass and Circulatory Arrest

  • Peter Pastuszko, Rady Children's Hospital of San Diego, San Diego, CA, United States
  • Afsaneh Pirzadeh, Department of Anesthesiology & Critical Care, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
  • Erin Reade, Department of Anesthesiology & Critical Care, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
  • Joanna Kubin, Department of Biochemistry & Biophysics, The University of Pennsylvania School of Medicine, Philadelphia, PA, United States
  • Alberto Mendoza, Department of Biochemistry & Biophysics, The University of Pennsylvania School of Medicine, Philadelphia, PA, United States
  • Gregory Schears, Department of Anesthesiology & Critical Care, Mayo Clinic, Rochester, MN, United States
  • William Greeley, Department of Anesthesiology & Critical Care, The Children’s Hospital of Philadelphia, Philadelphia, PA, United States
  • Anna Pastuszko, Department of Biochemistry & Biophysics, The University of Pennsylvania School of Medicine, Philadelphia, PA, United States

    • Objectives: Granulocyte colony-stimulating factor (G-CSF) has anti-inflammatory and anti-apoptotic properties. We investigated the effect of G-CSF on regulatory proteins involved in initiation (Bax) or inhibition (Jak-2 and Bcl-2) of apoptosis in the brain of newborn piglets following cardiopulmonary bypass and circulatory arrest.

    Methods: Anesthetized piglets were placed on CPB, cooled to 18°C, subjected to 30 min of DHCA and 1hr of LF at 20 ml/kg/min, rewarmed to 37°C and monitored for 6hrs. G-CSF was injected 2hr prior to bypass at 17 mg/kg (G-CSF-17) or 34 mg/kg (G-CSF-34). Protein expression is presented as % of no-G-CSF values (means (6) ± SE).

    Results: In striatum, Bcl-2 was higher by 73±4% (p<0.05) and 119±8% (p<0.01) in G-CSF-17 and G-CSF-34 groups, respectively. In GCSF-34 group Bax was lower by 19±3% (p<0.05) and Jak-2 was higher by 72±10% (p<0.05). Bcl-2/Bax ratio was 0.77, 1.16 and 1.99 in no-G-CSF, G-CSF-17, and GCSF-34 groups, respectively. Bcl-2/Bax increase suggests decreased susceptibility to apoptosis. In hippocampus, Bcl-2 was higher by 35±6% (p<0.05) and 137±11% (p<0.01) in the G-CSF-17 and G-CSF-34 groups, respectively. Bcl-2/Bax ratio was 0.68, 0.89 and 1.56 in no-G-CSF, G-CSF-17 and G-CSF-34 groups, respectively. Jak-2 increased 24±7% (p<0.05) in G-CSF-17 and 76±4% (p<0.01) in G-CSF-34 groups. In frontal cortex, Bcl-2 in the G-CSF-34 group increased 61±7% (p<0.05). Bcl-2/Bax ratio was 0.66, 0.64 and 1.0 in no-G-CSF, G-CSF-17 and G-CSF-34 groups, respectively.

    Conclusions: In the piglet model of circulatory arrest with low flow bypass, G-CSF provides significant protection, particularly in striatum and hippocampus, from apoptotic neuronal injury.