Granulocyte colony-stimulating factor has a negative effect on stroke outcome in a murine model.
The administration of CD34-positive cells after stroke has been shown to have a beneficial effect on functional recovery by accelerating angiogenesis and neurogenesis in rodent models. Granulocyte colony-stimulating factor (G-CSF) is known to mobilize CD34-positive cells from bone marrow and has displayed neuroprotective properties after transient ischemic stress. This led us to investigate the effects of G-CSF administration after stroke in mouse. We utilized permanent ligation of the M1 distal portion of the left middle cerebral artery to develop a reproducible focal cerebral ischemia model in CB-17 mice. Animals treated with G-CSF displayed cortical atrophy and impaired behavioral function compared with controls. The negative effect of G-CSF on outcome was associated with G-CSF induction of an exaggerated inflammatory response, based on infiltration of the peri-infarction area with CD11b-positive and F4/80-positive cells. Although clinical trials with G-CSF have been started for the treatment of myocardial and limb ischemia, our results indicate that caution should be exercised in applying these results to cerebral ischemia.
Taguchi
Akihiko
A
Department of Cerebrovascular Disease, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan, 565-8565. ataguchi@res.ncvc.go.jp
Wen
Zhongmin
Z
Myojin
Kazunori
K
Yoshihara
Tomoyuki
T
Nakagomi
Takayuki
T
Nakayama
Daisuke
D
Tanaka
Hidekazu
H
Soma
Toshihiro
T
Stern
David M
DM
Naritomi
Hiroaki
H
Matsuyama
Tomohiro
T
D000818:Animals; D001284:Atrophy; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D003627:Data Interpretation, Statistical; D004921:Erythropoietin / Q000627:therapeutic use; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007150:Immunohistochemistry; D051379:Mice; D020768:Middle Cerebral Artery / Q000502:physiology; D009336:Necrosis / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control; D011994:Recombinant Proteins; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology*; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor