G-CSF suppresses edema formation and reduces interleukin-1beta expression after cerebral ischemia in mice.
Granulocyte-colony stimulating factor (G-CSF) is reported to be neuroprotective after transient cerebral ischemia with respect to decreasing lesion volume and enhancing functional recovery. We investigated whether G-CSF is neuroprotective after permanent ischemia and the possible mechanisms underlying this neuroprotection. Mice underwent permanent or 60-minute middle cerebral artery occlusion (MCAO) and received G-CSF (50 microg/kg) or vehicle at the onset or 1 hour post-MCAO. Forty-eight hours after transient MCAO, structural magnetic resonance imaging revealed a significant reduction (50%) in the amount of edematous tissue present in G-CSF-treated mice (p < 0.05). G-CSF treatment also prevented a significant increase in ipsilateral brain water content that was present in vehicle-treated mice after transient (p < 0.05) and permanent (p < 0.001) MCAO. Forty-eight hours after permanent MCAO, G-CSF decreased (50%) the cortical lesion volume (p < 0.05). Using real-time polymerase chain reaction, we found that G-CSF treatment significantly suppressed (p < 0.05) the injury-induced upregulation of IL-1beta mRNA while having no effect on TNFalpha and NOS-2 mRNA expression. This suggests that part of the neuroprotection may be attributed to the ability of G-CSF to reduce the inflammatory response.
Gibson
Claire L
CL
Institute of Cell Signalling, University of Nottingham, UK.
Jones
Nigel C
NC
Prior
Malcolm J W
MJ
Bath
Philip M W
PM
Murphy
Sean P
SP
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001929:Brain Edema / Q000517:prevention & control*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D015870:Gene Expression; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000096:biosynthesis*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects
D029742:Caenorhabditis elegans Proteins; D007375:Interleukin-1; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C400703:nos-2 protein, C elegans; D016179:Granulocyte Colony-Stimulating Factor