title: Granulocyte colony-stimulating factor enhances the angiogenetic effect of indirect bypass surgery for chronic cerebral hypoperfusion in a rat model.
abstract: BACKGROUND
  Granulocyte colony-stimulating factor (G-CSF) mobilizes hematopoietic bone marrow cells into systemic circulation and has been used clinically to treat chemotherapy-induced neutropenia. Recently, G-CSF was shown to have neuroprotective and angiogenetic effects in acute cerebral infarction.
  
  
  OBJECTIVE
  To evaluate the effects of G-CSF for angiogenesis after indirect bypass surgery.
  
  
  METHODS
  : Chronic cerebral hypoperfusions were induced in male Wistar rats by permanent bilateral internal carotid artery occlusion (BICAO). After BICAO, unilateral indirect bypass and encephalogaleosynangiosis (EGS) were performed, and human recombinant G-CSF (10 μg/kg) or saline was injected intramuscularly for 5 consecutive days. We measured regional cerebral blood flow (rCBF) by laser Doppler flowmetry and performed immunohistochemical analysis 21 days after BICAO.
  
  
  RESULTS
  BICAO decreased rCBF to 62.52% ± 5.8% of control (P < .01). The rCBF increased significantly 21 days after BICAO in all treatment groups (n = 10; P < .05) except the G-E- group. The rCBF increase observed in the G+E+ group was significantly higher than that observed in other groups. Both G-CSF and EGS treatments significantly increased the number of small vessels (P < .01), and G-CSF and EGS showed additive effect in increasing the number of small vessels.
  
  
  CONCLUSIONS
  Combined use of G-CSF and indirect bypass surgery induces an increase in rCBF and angiogenesis under conditions of cerebral chronic hypoperfusion. This is the first report to demonstrate that G-CSF can enhance angiogenesis induced by indirect bypass surgery, and that this combined therapy is a safe and easy method of treatment.
authors.affiliation: Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohmori
authors.forename: Motohiro
authors.initials: M
authors.lastname: Morioka
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kaku
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawano
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kuratsu
mesh_terms: D042501:Angiogenic Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery*; D002548:Cerebral Revascularization / Q000379:methods*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D042501:Angiogenic Proteins; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000069585:Filgrastim