G-CSF and its receptor are induced by cerebral ischemia. (A–C) Quantitative PCR demonstrates induction of mRNA following cerebral ischemia. (A) In the MCAO model, G-CSF mRNA is induced more than 100-fold in the ipsilateral and contralateral forebrain hemisphere at 2 hours following ischemia. At 6 hours, induction levels dropped, and overexpression became more specific to the ipsilateral hemisphere. At 20 hours, induction was no longer detectable (data not shown). (B) Moderate induction of the G-CSF receptor mRNA in forebrain hemispheres was seen 6 hours following MCAO. (C) Receptor induction was also detected 6 hours after ischemia in another ischemic model, cortical photothrombotic ischemia in biopsy material from the periinfarct cortex. The substantially higher induction reflects the strong induction in the infarct penumbral zone. (D–O) Immunohistochemical detection of receptor and ligand in the corresponding ischemia models. (D–I) Staining for G-CSF receptor (D–F) and ligand (G–I) in the MCAO model, 6 hours after ischemia: ipsilateral cortex (D and G) and corresponding areas of the contralateral hemisphere (E and H) and the cortex of a sham-operated rat (F and I). (J–O) Staining for G-CSF receptor (J–L) and G-CSF itself (M–O) in the photothrombotic model: ipsilateral cortex (J and M) and corresponding areas of the contralateral hemisphere (K and N) and the cortex of a sham-operated rat (L and O). The infarct border zone is shown in the upper-right quadrant in D, G, J, and M and is particularly clear in the photothrombotic model. Note the strong dendritic staining for the G-CSFR. Original magnification ×20.