title: Effects of G-CSF treatment on neutrophil mobilization and neurological outcome after transient focal ischemia.
abstract: Several recent studies demonstrated beneficial effects of G-CSF treatment (granulocyte colony-stimulating factor) in various CNS disease. Possible mechanisms underlying this activity are neuroprotection, anti-apoptosis, angiogenesis and anti-inflammation. Hence, we investigated the efficacy of G-CSF administration in experimental stroke by determining infarct volume and neurological score in wildtype, G-CSF-deficient and G-CSF-treated G-CSF-deficient mice. Besides, cerebral ischemia is followed by an upregulation of endothelial adhesion molecules which promote leukocyte recruitment to the injured area. In combination with G-CSF-induced leukocytosis, increased peripheral neutrophils could aggregate within microvasculature and additionally impair blood perfusion of the ischemic tissue. Therefore, we analyzed the neutrophil counts in both vessel and tissue compartment 2 and 5 days post-stroke by immunohistochemistry. Here we show that G-CSF deficiency leads to increased infarct volumes, whereas G-CSF substitution revokes detrimental effects by reducing lesion size and enhancing neurological outcome compared to untreated animals. Administration of G-CSF is accompanied by significant increase of circulating neutrophils 2 days post-ischemia but leukocytosis is restricted to the vessel compartment and has no deleterious effect on lesion formation and functional recovery. These observations are likely to be important for therapeutic targeting of G-CSF-mediated neuroprotection in stroke.
authors.affiliation: Department of Neurology, University of Münster, Albert-Schweitzer Str. 33, 48129 Münster, Germany. strecker.jan@gmx.de
authors.forename: Jan-Kolja
authors.initials: JK
authors.lastname: Strecker
authors.forename: Sevgi
authors.initials: S
authors.lastname: Sevimli
authors.forename: Matthias
authors.initials: M
authors.lastname: Schilling
authors.forename: Rainer
authors.initials: R
authors.lastname: Klocke
authors.forename: Sigrid
authors.initials: S
authors.lastname: Nikol
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D020520:Brain Infarction / Q000188:drug therapy; D002465:Cell Movement / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009460:Neurologic Examination / Q000379:methods; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014841:von Willebrand Factor
chemical_list: D000906:Antibodies; D007211:Indoles; D014841:von Willebrand Factor; D016179:Granulocyte Colony-Stimulating Factor; C007293:DAPI