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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

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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 h 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 h 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.

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Acknowledgments

This study was supported by NIH grant R01NS060936 to J. Tang

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Authors and Affiliations

  1. Department of Physiology & Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA

    Desislava Doycheva, Hank Chen, John H. Zhang & Jiping Tang

  2. Department of Anaesthesiology, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA

    Gary Shih & Richard Applegate

  3. Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA, 92354, USA

    John H. Zhang

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  1. Desislava Doycheva
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Correspondence to Jiping Tang.

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Doycheva, D., Shih, G., Chen, H. et al. 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. Transl. Stroke Res. 4, 171–178 (2013). https://doi.org/10.1007/s12975-012-0225-2

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