Potentiation of neurogenesis and angiogenesis by G-CSF after focal cerebral ischemia in rats.
Recently, granulocyte colony-stimulating factor (G-CSF) is expected to demonstrate beneficial effects on cerebral ischemia. Here, we showed the potential benefit of G-CSF administration after transient middle cerebral artery occlusion (tMCAO). Adult male Wistar rats received vehicle or G-CSF (50 microg/kg) subcutaneously after reperfusion, and were treated with 5-bromodeoxyuridine (BrdU, 50 mg/kg) once daily by the intraperitoneal route for 3 days after tMCAO. Nissl-stained sections at 7 days after tMCAO showed significant reduction of the infarction area (31%, P<0.01). At 7 days after tMCAO, BrdU plus NeuN double-positive cells increased by 43.3% in the G-CSF-treated group (P<0.05), and BrdU-positive endothelial cells were increased 2.29 times in the G-CSF-treated group, to a level as high as that in the vehicle-treated group (P<0.01), in the periischemic area. Our results indicate that G-CSF caused potentiation of neuroprotection and neurogenesis and is expected to have practical therapeutic potential in treating individuals after ischemic brain injury.
Sehara
Yoshihide
Y
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama, 700-8558, Japan.
Hayashi
Takeshi
T
Deguchi
Kentaro
K
Zhang
Hanzhe
H
Tsuchiya
Atsushi
A
Yamashita
Toru
T
Lukic
Violeta
V
Nagai
Makiko
M
Kamiya
Tatsushi
T
Abe
Koji
K
D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D013997:Time Factors
D005904:Glial Fibrillary Acidic Protein; D016179:Granulocyte Colony-Stimulating Factor; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine