Induction of granulocyte colony-stimulating factor mRNA by focal cerebral ischemia and cortical spreading depression.
Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with neuroprotective and antiinflammatory properties. By real-time polymerase chain reaction we show that G-CSF transcripts are induced 485-fold at 4 h and 65-fold at 16 h in ischemic lesions after middle cerebral artery occlusion compared to control brains. Further analysis in photochemically induced focal ischemia revealed that G-CSF induction involved both the infarct area and remote nonischemic brain regions. Remote responses could be blocked by the noncompetitive NMDA receptor antagonist MK-801, suggesting periinfarct depolarizations as a trigger. To further confirm this notion, cortical spreading depression (CSD) was induced by focal application of KCl to the brain surface. CSD led to a 90-fold increase in G-CSF mRNA. Contrastingly, the induction of granulocyte-monocyte (GM)-CSF, another member of the hematopoietic growth factor family, was only moderate (sixfold) and restricted to ischemic brain lesions. In conclusion, G-CSF induction in the brain may be part of an intrinsic stress response aimed at limitation of neuronal damage.
Kleinschnitz
Christoph
C
Department of Neurology, Julius-Maximilians Universität, Josef-Schneider-Str. 11, D-97080 Würzburg, Germany.
Schroeter
Michael
M
Jander
Sebastian
S
Stoll
Guido
G
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor