Granulocyte-colony stimulating factor in combination with stem cell factor confers greater neuroprotection after hypoxic-ischemic brain damage in the neonatal rats than a solitary treatment.

Abstract

Neonatal hypoxia-ischemia (HI) is a devastating condition resulting in neuronal cell death and often culminates in neurological deficits. Granulocyte-colony stimulating factor (G-CSF) has been shown to have neuroprotective activity via inhibition of apoptosis and inflammation in various stroke models. Stem cell factor (SCF) regulates hematopoietic stem cells in the bone marrow and has been reported to have neuroprotective properties in an experimental ischemic stroke model. In this study we aim to determine the protective effects of G-CSF in combination with SCF treatment after experimental HI. Seven-day old Sprague-Dawley rats were subjected to unilateral carotid artery ligation followed by 2.5 hours of hypoxia. Animals were randomly assigned to five groups: Sham (n=8), Vehicle (n=8), HI with G-CSF treatment (n=9), HI with SCF treatment (n=9) and HI with G-CSF+SCF treatment (coadministration group; n=10). G-CSF (50 µg/kg), SCF (50 µg/kg) and G-CSF+SCF (50 µg/kg) were administered intraperitoneally 1 hour post HI followed by daily injection for 4 consecutive days (five total injections). Animals were euthanized 14 days after HI for neurological testing. Additionally assessment of brain, heart, liver, spleen and kidney atrophy was performed. Both G-CSF and G-CSF+SCF treatments improved body growth and decreased brain atrophy at 14 days post HI. No significant differences were found in the peripheral organ weights between groups. Finally, the G-CSF+SCF coadministration group showed significant improvement in neurological function. Our data suggest that administration of G-CSF in combination with SCF not only prevented brain atrophy but also significantly improved neurological function.

• Authors: Desislava Doycheva, Gary Shih, Hank Chen, Richard Applegate, John H Zhang, Jiping Tang
• Journal: Translational stroke research (Transl Stroke Res) Vol. 4 Issue 2 Pg. 171-8 (Apr 2013) ISSN: 1868-601X [Electronic] United States
• PMID: 23565130 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Neuroprotective Agents
• Stem Cell Factor
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Animals, Newborn
• Apoptosis
• Disease Models, Animal
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Hypoxia-Ischemia, Brain (pathology)
• Neuroprotective Agents (administration & dosage)
• Rats
• Rats, Sprague-Dawley
• Stem Cell Factor (administration & dosage)