An extended window of opportunity for G-CSF treatment in cerebral ischemia.
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.
Schneider
Armin
A
Axaron Bioscience AG, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany. schneider@axaron.de
Wysocki
Rainer
R
Pitzer
Claudia
C
Krüger
Carola
C
Laage
Rico
R
Schwab
Stefan
S
Bach
Alfred
A
Schäbitz
Wolf-Rüdiger
WR
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
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor