Granulocyte-Colony Stimulating Factor Delays PWI/DWI Mismatch Evolution and Reduces Final Infarct Volume in Permanent-Suture and Embolic Focal Cerebral Ischemia Models in the Rat

Abstract

Background and Purpose— Granulocyte-colony stimulating factor (G-CSF) is used clinically to attenuate neutropenia after chemotherapy. G-CSF acts as a growth factor in the central nervous system, counteracts apoptosis, and is neuroprotective in rodent transient ischemia models. Methods— We assessed the effect of G-CSF on ischemic lesion evolution in a rat permanent-suture occlusion model with diffusion- and perfusion-weighted magnetic resonance imaging and the neuroprotective effect of G-CSF in a rat embolic stroke model. Results— With a constant perfusion deficit, vehicle-treated animals showed an expanding apparent diffusion coefficient lesion volume that matched the perfusion deficit volume at ≈3 hours, with the 24-hour infarct volume equivalent to the perfusion deficit. In G-CSF–treated rats, the apparent diffusion coefficient lesion volume did not increase after treatment initiation, and the infarct volume at 24 hours reflected the initial apparent diffusion coefficient lesion volume. In the embolic model, we observed a significant decrease in infarct volume in G-CSF–treated animals compared with the vehicle-treated group. Conclusions— These results confirm the potent neuroprotective activity of G-CSF in different focal ischemia models. The magnetic resonance imaging data demonstrate that G-CSF preserved the perfusion/diffusion mismatch.