Granulocyte-colony stimulating factor (G-CSF) and G-CSF receptor expression in human ischemic stroke

摘要

Granulocyte-colony stimulating factor (G-CSF) receptor signaling counteracts detrimental pathways in ischemic stroke. In rodents, neuroprotection provided by the G-CSF system involves up-regulation of the G-CSF receptor and its ligand, G-CSF, during cerebral ischemia. The confirmation of a similar response in the human brain would be an important rationale for the use of G-CSF in clinical stroke trials. Therefore, the temporal and cellular profile of G-CSF and G-CSF receptor expression was examined in a series of human stroke brains. The median age of the 21 stroke patients was 67 years; median time from death to autopsy was 24 h (range: 10–67 h). In acute ischemic stroke, strong neuronal G-CSF receptor immunoreactivity was encountered in the infarct area and the peri-infarct rim as compared to the contralateral cortex. In subacute infarctions, microglial and macrophage G-CSF receptor immunoreactivity predominated, whereas chronic infarction was characterized by the presence of G-CSF receptor expressing reactive astrocytes. Neuronal G-CSF expression was encountered very early upon ischemic stroke. At later time-points, an up-regulation of vascular G-CSF expression in the peri-infarct area prevailed. In conclusion, the observed up-regulation of G-CSF receptors and G-CSF points towards a role in the pathophysiology of human ischemic stroke.