G-CSF has stable neuroprotective activity in focal cerebral ischemia and passes the intact BBB. (A) G-CSF has efficacy in the transient MCAO stroke model when given 2 hours after onset of ischemia, as shown by reduction in infarct volume (dose: 60 μg/kg i.v.; vehicle, n = 7; G-CSF, n = 10; **P < 0.01 by 2-sided t test). (B) G-CSF reduces infarct volume in the rat cortical combined CCA/distal MCA occlusion model when given 1 hour after onset of ischemia (dose: 50 μg/kg i.v.; n = 5 each; *P < 0.05). (C) Behavioral measurements in the cortical combined CCA/distal MCA occlusion model. G-CSF–treated animals have a better composite neurological deficit score (NDS) (*P < 0.05). (D) Comparison of the brain/serum ratios of i.v. injected iodinated G-CSF and albumin at 1, 4, and 24 hours following injection. Albumin does not pass the BBB. Radiolabeled proteins (G-CSF and BSA) were injected via the tail vein of healthy female Sprague-Dawley rats. The relative amount of radiolabeled G-CSF and BSA in serum and brain was measured, and the ratio of brain/serum was plotted against the time. The brain/serum ratio of G-CSF was significantly greater than that of albumin, which indicated passage of the intact BBB in non-ischemic animals.