G-CSF administration is neuroprotective following transient cerebral ischemia even in the absence of a functional NOS-2 gene.
Granulocyte colony-stimulating factor (G-CSF) is a candidate neuroprotective factor following cerebral ischemia. To determine whether G-CSF acts partly through the inhibition of nitric oxide synthase (NOS)-2 expression, we administered G-CSF to male NOS-2-/- mice after cerebral ischemia. Although male NOS-2-/- mice exhibit resistance to the gross effects of cerebral ischemia, they display neuronal loss and skilled motor deficits following cerebral ischemia. Administration of G-CSF during reperfusion reduced motor deficit and neuronal loss. Thus, G-CSF is still effective in NOS-2 gene-deficient mice, suggesting that part of the mechanism of action is independent of NOS-2.
Institute of Neuroscience, University of Nottingham, Nottingham, UK. cg95@le.ac.uk
Claire L
CL
Gibson
Philip M W
PM
Bath
Sean P
SP
Murphy
D000818:Animals; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045442:Rotarod Performance Test
D018696:Neuroprotective Agents; D016179:Granulocyte Colony-Stimulating Factor; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse