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

Desislava Doycheva, Gary Shih, Hank Chen, Richard Lee Applegate, John H. Zhang, Jiping Tang

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)171-178
Number of pages8
JournalTranslational Stroke Research
Volume4
Issue number2
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Brain Hypoxia
Stem Cell Factor
Granulocyte Colony-Stimulating Factor
Ischemia
Atrophy
Therapeutics
Brain
Stroke
Neuroprotection
Hypoxia
Injections
Organ Size
Hematopoietic Stem Cells
Carotid Arteries
Ligation
Sprague Dawley Rats
Cell Death
Spleen
Bone Marrow
Apoptosis

Keywords

  • Granulocyte-colony stimulating factor (G-CSF)
  • Hypoxia-ischemia (HI)
  • Neurological outcome
  • Stem cell factor (SCF)

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Cardiology and Cardiovascular Medicine

Cite this

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. / Doycheva, Desislava; Shih, Gary; Chen, Hank; Applegate, Richard Lee; Zhang, John H.; Tang, Jiping.

In: Translational Stroke Research, Vol. 4, No. 2, 2013, p. 171-178.

Research output: Contribution to journalArticle

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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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