G-CSF administration to adult mice stimulates the proliferation of microglia but does not modify the outcome of ischemic injury

Recent evidence suggests that adult bone marrow stem cells reduce tissue damage and promote repair following CNS ischemic injury. Since granulocyte-colony stimulating factor (G-CSF) mobilizes hematopoietic stem cells to the circulating compartment, here we tested whether administration of this drug modifies the outcome of a permanent occlusion of the middle cerebral artery in adult mice. To elucidate the behavior and fate of blood-borne cells in the ischemic brain, we produced chimeric animals, in which hematopoietic derivatives are genetically tagged. G-CSF administration enhances the proliferation of microglia in the uninjured CNS but has no effect on the amount of hematopoietic cells that infiltrate the ischemic tissue and on the size of the lesion. The blood-borne elements acquire different mesodermal identities but fail to adopt neural phenotypes, even though they occasionally fuse with Purkinje neurons. These results indicate that G-CSF treatment does not exert a significant beneficial effect on the ischemic injury.

Research Highlights
► Granulocyte-colony Stimulating Factor (G-CSF) mobilizes hematopoietic stem cells to circulating blood.
► We asked whether G-CSF exerts beneficial effects on CNS ischemic injury.
► In the intact mouse CNS, G-CSF stimulates proliferation of microglia.
► Following ischemic injury, G-CSF.
• Does not enhance infiltration of blood-borne cells.
• Does not modify the fate of infiltrating cells.
• Does not reduce the extent of the ischemic injury.
► Albeit effective on the CNS, G-CSF does not modify the outcome of ischemic injury.