Granulocyte colony-stimulating factor enhances anglogenesis after focal cerebral ischemia

Granulocyte colony-stimulating factor (G-CSF) is a neuroprotective agent and activates endothelial proliferation and bone marrow stem cell mobilization. We studied the effect of G-CSF on angiogenesis and neurological recovery after focal cerebral ischemia. After the induction of transient focal ischemia in rats, G-CSF (50 mu g/kg/day, i.p.) or PBS was administered for 3 days. We evaluated the functional recovery, infarct volume, inflammatory infiltration, blood-brain barrier (131313) disruption, hemispheric atrophy, protein expressions of endothelial nitric oxide synthase (eNOS) and angiopoietins, and the therapeutic time window of G-CSF administration. We then analyzed enclothelial cell proliferation, the vascular surface area, the number of branch points, and the vascular length. G-CSF treatment improved behavioral recovery and reduced the infarct volume, the inflammatory infiltration, the 131313 disruption, and the hemispheric atrophy. G-CSF injection, starting at 2 h, I day, or 4 days after ischemia, resulted in a better functional recovery and a greater reduction in hemispheric atrophy than injection starting at day 7. The vascular surface area, the vascular branch points, the vascular length, the number of BrdU(+) endothelial cells, and eNOS/ angiopoietin-2 expression were significantly increased in the G-CSF group compared with the ischemia-only group. G-CSF injection starting at I day induced larger endothelial proliferation compared with injection starting at 7 days. In this study, we provide evidences that G-CSF enhances the angiogenesis and reduces the ischemic damage, which promotes the long-term functional recovery. (c) 2005 Elsevier B.V. All rights reserved.