title: Granulocyte colony-stimulating factor fails to enhance leptomeningeal collateral growth in spontaneously hypertensive rats.
abstract: The promotion of collateral artery growth is an attractive approach for the treatment of chronic brain hypoperfusion due to occlusive artery disease. We previously reported that hypertension impaired the collateral artery growth of leptomeningeal anastomoses after brain hypoperfusion. Granulocyte colony-stimulating factor (G-CSF) enhances arteriogenesis in a mouse model via a mechanism involving monocyte/macrophage mobilization. However, the arteriogenic effect of G-CSF in hypertension remains unknown. In the present study, we tested whether G-CSF affected collateral artery growth in both normotensive and hypertensive model rat. Left common carotid artery (CCA) occlusion was performed to induce hypoperfusion in the brains of Wistar rats and spontaneously hypertensive rats (SHR). G-CSF was administered subcutaneously for 5 consecutive days. The superficial angioarchitecture of the leptomeningeal anastomoses and the circle of Willis after CCA occlusion and G-CSF treatment were visualized by latex perfusion. Circulating blood monocytes and CD68-positive cells, which represented the macrophages on the dorsal surface of the brain, were counted. G-CSF enhanced leptomeningeal collateral growth in Wistar rats, but not in SHR. G-CSF increased circulating blood monocytes in both Wistar rats and SHR. The number of CD68-positive cells on the dorsal surface of the brain was increased by G-CSF in Wistar rats, but not in SHR. The increase in macrophage accumulation correlated with the observed arteriogenic effects. In conclusion, G-CSF promotes collateral artery growth in the normotensive model rat, but not in the hypertensive model rat.
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Yukio
authors: Y
authors: Sugiyama
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan. Electronic address: yagita@neurol.med.osaka-u.ac.jp.
authors: Yoshiki
authors: Y
authors: Yagita
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Toshiro
authors: T
authors: Yukami
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Akihiro
authors: A
authors: Watanabe
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Naoki
authors: N
authors: Oyama
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Yasukazu
authors: Y
authors: Terasaki
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Emi
authors: E
authors: Omura-Matsuoka
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Tsutomu
authors: T
authors: Sasaki
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hideki
authors: H
authors: Mochizuki
authors: Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Kazuo
authors: K
authors: Kitagawa
mesh_terms: D000818:Animals; D001163:Arteriovenous Anastomosis / Q000187:drug effects; D020212:Carotid Artery Injuries / Q000503:physiopathology; D002941:Circle of Willis / Q000187:drug effects; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008578:Meninges / Q000098:blood supply* / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: Arteriogenesis; Brain hypoperfusion; Granulocyte colony-stimulating factor