Systemic application of granulocyte-colony stimulating factor and stem cell factor exacerbates excitotoxic brain injury in newborn mice

Pediatr Res. 2006 Apr;59(4 Pt 1):549-53. doi: 10.1203/01.pdr.0000205152.38692.81.


Granulocyte-colony stimulating factor (G-CSF) has been shown to reduce brain lesion size and mortality in adult mice after hypoxic-ischemic injury. Another hematopoietic growth factor, stem cell factor (SCF), has been shown to be up-regulated in the brains of adult rodents following brain damage, where it stimulates postlesional neurogenesis. Injection of the excitotoxic agent ibotenate into the brain of newborn mice produces a brain lesion characterized by neuronal death and white matter cysts, which is similar to periventricular leucomalacia. The aim of the present study was to investigate whether administration of SCF and G-CSF is neuroprotective against ibotenate lesions in neonatal mice. Contrary to our expectations, cortical and white matter brain lesions induced by ibotenate were enhanced following the administration of 50 microg/kg SCF or 200 microg/kg G-CSF. Dose-response studies indicated that G-CSF could increase grey matter lesions even at lower dosages (22 and 66 microg/kg). Administration of SCF and G-CSF in combination also increased cortical and white matter lesions, to 133 +/- 8% and 187 +/- 12%. In the undamaged brain, G-CSF or G-CSF+SCF treatment had no effect on apoptosis in the grey or white matter; however, these treatments significantly increased apoptosis in the damaged brain. Our data clearly demonstrate that G-CSF and SCF are not neuroprotective and result in deleterious enhancement of excitotoxic brain damage in newborn mice. We conclude that G-CSF and SCF should be used cautiously in newborn infants with brain lesions; if they are used, long term neurologic and neurodevelopmental follow-up is warranted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis
  • Brain / cytology
  • Brain / drug effects
  • Brain / pathology
  • Brain Injuries / chemically induced*
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Agonists / toxicity*
  • Granulocyte Colony-Stimulating Factor* / metabolism
  • Granulocyte Colony-Stimulating Factor* / pharmacology
  • Ibotenic Acid / toxicity*
  • Mice
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Neurotoxins / toxicity*
  • Stem Cell Factor* / metabolism
  • Stem Cell Factor* / pharmacology


  • Excitatory Amino Acid Agonists
  • Neuroprotective Agents
  • Neurotoxins
  • Stem Cell Factor
  • Granulocyte Colony-Stimulating Factor
  • Ibotenic Acid