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Granulocyte colony-stimulating factor enhances angiogenesis after focal cerebral ischemia
Cited 146 time in
Web of Science
Cited 167 time in Scopus
- Authors
- Issue Date
- 2005-09-10
- Publisher
- Elsevier
- Citation
- Brain Res. 2005 Oct 5;1058(1-2):120-8. Epub 2005 Sep 8.
- Keywords
- Angiopoietin-1/analogs & derivatives/metabolism ; Animals ; Atrophy/drug therapy/pathology/physiopathology ; Blood-Brain Barrier/drug effects/physiology ; Brain/blood supply/*drug effects/physiopathology ; Brain Infarction/drug therapy/pathology/physiopathology ; Brain Ischemia/*drug therapy/pathology/physiopathology ; Cell Proliferation/drug effects ; Cerebral Arteries/*drug effects/physiology ; Drug Administration Schedule ; Encephalitis/etiology/pathology/physiopathology ; Endothelial Cells/drug effects/physiology ; Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology/therapeuticuse ; Male ; Neovascularization, Physiologic/*drug effects/physiology ; Neuroprotective Agents/pharmacology/therapeutic use ; Nitric Oxide Synthase Type III/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Recovery of Function/drug effects/physiology ; Treatment Outcome
- 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.
- ISSN
- 1872-6240 (Electronic)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16150422
https://hdl.handle.net/10371/15844
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