Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia

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Lee, Soon-Tae; Chu, Kon; Jung, Keun-Hwa; Ko, Song-Yi; Kim, Eun-Hee; Sinn, Dong In; Lee, Yong Seok; Lo, Eng H; Kim, Manho; Roh, Jae Kyu
Issue Date
Brain Res. 2005 Oct 5;1058(1-2):120-8. Epub 2005 Sep 8.
Angiopoietin-1/analogs & derivatives/metabolismAnimalsAtrophy/drug therapy/pathology/physiopathologyBlood-Brain Barrier/drug effects/physiologyBrain/blood supply/*drug effects/physiopathologyBrain Infarction/drug therapy/pathology/physiopathologyBrain Ischemia/*drug therapy/pathology/physiopathologyCell Proliferation/drug effectsCerebral Arteries/*drug effects/physiologyDrug Administration ScheduleEncephalitis/etiology/pathology/physiopathologyEndothelial Cells/drug effects/physiologyGranulocyte-Macrophage Colony-Stimulating Factor/*pharmacology/therapeuticuseMaleNeovascularization, Physiologic/*drug effects/physiologyNeuroprotective Agents/pharmacology/therapeutic useNitric Oxide Synthase Type III/drug effects/metabolismRatsRats, Sprague-DawleyRecovery of Function/drug effects/physiologyTreatment Outcome
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.
1872-6240 (Electronic)
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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