title: An extended window of opportunity for G-CSF treatment in cerebral ischemia.
abstract: BACKGROUND
  Granulocyte-colony stimulating factor (G-CSF) is known as a powerful regulator of white blood cell proliferation and differentiation in mammals. We, and others, have shown that G-CSF is effective in treating cerebral ischemia in rodents, both relating to infarct size as well as functional recovery. G-CSF and its receptor are expressed by neurons, and G-CSF regulates apoptosis and neurogenesis, providing a rational basis for its beneficial short- and long-term actions in ischemia. In addition, G-CSF may contribute to re-endothelialisation and arteriogenesis in the vasculature of the ischemic penumbra. In addition to these trophic effects, G-CSF is a potent neuroprotective factor reliably reducing infarct size in different stroke models.
  
  
  RESULTS
  Here, we have further delayed treatment and studied effects of G-CSF on infarct volume in the middle cerebral artery occlusion (MCAO) model and functional outcome in the cortical photothrombotic model. In the MCAO model, we applied a single dose of 60 microg/kg bodyweight G-CSF in rats 4 h after onset of ischemia. Infarct volume was determined 24 h after onset of ischemia. In the rat photothrombotic model, we applied 10 microg/kg bodyweight G-CSF daily for a period of 10 days starting either 24 or 72 h after induction of ischemia. G-CSF both decreased acute infarct volume in the MCAO model, and improved recovery in the photothrombotic model at delayed timepoints.
  
  
  CONCLUSIONS
  These data further strengthen G-CSF's profile as a unique candidate stroke drug, and provide an experimental basis for application of G-CSF in the post-stroke recovery phase.
authors.affiliation: Axaron Bioscience AG, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany. schneider@axaron.de
authors.forename: Armin
authors.initials: A
authors.lastname: Schneider
authors.forename: Rainer
authors.initials: R
authors.lastname: Wysocki
authors.forename: Claudia
authors.initials: C
authors.lastname: Pitzer
authors.forename: Carola
authors.initials: C
authors.lastname: Krüger
authors.forename: Rico
authors.initials: R
authors.lastname: Laage
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwab
authors.forename: Alfred
authors.initials: A
authors.lastname: Bach
authors.forename: Wolf-Rüdiger
authors.initials: WR
authors.lastname: Schäbitz
mesh_terms: D000818:Animals; D002544:Cerebral Infarction / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor