title: Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia.
abstract: 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 micro/day, i.p.) or PBS was administered for 3 days. We evaluated the functional recovery, infarct volume, inflammatory infiltration, blood-brain barrier (BBB) 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 endothelial 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 BBB disruption, and the hemispheric atrophy. G-CSF injection, starting at 2 h, 1 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 1 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.
authors.affiliation: Department of Neurology, Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Stem Cell Research Center, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Song-Yi
authors.initials: SY
authors.lastname: Ko
authors.forename: Eun-Hee
authors.initials: EH
authors.lastname: Kim
authors.forename: Dong In
authors.initials: DI
authors.lastname: Sinn
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Eng H
authors.initials: EH
authors.lastname: Lo
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Jae Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D042683:Angiopoietin-1 / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D020520:Brain Infarction / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D004660:Encephalitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D042683:Angiopoietin-1; C467629:Angpt1 protein, rat; D018696:Neuroprotective Agents; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D052250:Nitric Oxide Synthase Type III