Effect of systemic administration of GCSF/SCF or FL on hypoxic/hyperoxic ischemic brain injury in newborn mice

Abstract

Objective Hypoxic ischemic injury plays an important role in the pathogenesis of preterm brain damage. We have shown that granulocyte colony stimulating factor (GCSF) and stem cell factor (SCF) increase excitotoxic brain injury in newborn mice, when administered in the acute phase of the insult. Administration after the acute phase significantly reduces the injury. The aim of this study was to evaluate the effect of haematopoietic growth factors (GCSF/SCF and Fms like tyrosine kinase 3 ligand (FL)) in a neonatal model of hypoxic/hyperoxic ischemic (HHI) brain injury. Methods Unilateral carotid artery ligation was performed in mice on postnatal day 5 (P5) followed by hypoxia (8% O2) for 15 min alternating with hyperoxia (100% O2) for 10 min, totally 65 min. 60 hours later i) GCSF/SCF, ii) FL or iii) vehicle was randomly injected intraperitoneally repetitively every 24 hours, 3 or 5 times. Endpoints were set at P10, P21 and P120, histological and neurobehavioral outcome was anlayzed. Results HHI resulted in a moderate to severe brain injury with white matter cysts and cortical atrophy. Although there were animals which seemed to benefit (in terms of lesion size and outcome) from these treatments, this did not reach statistical significance. Conclusion In the excitotoxic injury model the same treatment regimen reduced brain damage. Thus we speculate that the effect of these treatments strongly depends on the severity of brain injury. Thus in severe damage with great tissue loss, the “matrix” (e.g. cells secreting chemoattractants) required for neuroregeneration might be lost.