Central administration of granulocyte-colony stimulating factor in a mice middle cerebral artery occlusion stroke model reduces infarct volume and improves functional outcome

Abstract

Granulocyte-colony stimulating factor (G-CSF), a 20 kDa glycoprotein, has a role in promoting survival, proliferation and differentiation of hematopoietic cells. Recent studies have shown that G-CSF exhibits beneficial effects after cerebral ischemia. G-CSF may confer direct neuroprotection through its non-hematopoietic effects and/or indirect benefits via mobilization of the stem/progenitor cells from the bone marrow into the brain via peripheral blood. In this study, we aim to determine if G-CSF has any direct neuroprotective effects in the mice stroke model. Mice were subjected to transient focal middle cerebral artery occlusion (MCAO) for 60 minutes. A single dose of G-CSF (5 µg/kg, 1 µg/kg, 0.2 µg/kg) or vehicle (saline) at 1µL was given via an intrastriatal injection over 5 minutes commenced at the beginning of reperfusion. The WBC count in the peripheral blood was checked before and after (at 24 hr and 72 hr) the cytokine injection. The mice were decapitated at 72 hr and their brains were cut into 2-mm thick coronal slices before reaction with a 2% solution of 2,3,5-triphenyltetrazolium chloride to reveal the infarct. G-CSF did not change the peripheral WBC level at 24 hr and 72 hr (P>0.05 versus control). Treatment with G-CSF significantly reduced the infarct volumes at the doses of 5 µg/kg (34%, P<0.01) and 1 µg/kg (35%, P<0.01) but not 0.2 µg/kg (P>0.05). Also, better functional performances were seen in the G-CSF-treated groups in turning in an alley (5 µg/kg, P<0.05 and 1 µg/kg, P<0.05) as well as the hanging wire test (5 µg/kg, P<0.01 and 1 µg/kg, P<0.01) when compared with that in the vehicle-treated group. Our results indicate that G-CSF exerts direct neuroprotective effect through its non-hematopoietic effects, and further studies are needed to understand the mechanisms of this action.