Multiparametric assessment of acute and subacute ischemic neuronal damage: a small animal positron emission tomography study with rat photochemically induced thrombosis model.

We evaluated sequential changes in rat brain function up to 14 days after focal ischemic insult with a small animal positron emission tomography (PET). Unilateral focal ischemic cerebral damage was induced by left middle cerebral artery occlusion with a photochemically induced thrombosis (PIT) method. PET scans were conducted with [(11)C](R)-PK11195 ([(11)C](R)-PK) for peripheral benzodiazepine receptor (PBR), [(11)C]flumazenil ([(11)C]FMZ) for central benzodiazepine receptor (CBR), and [(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) for glucose metabolism at before (as "Normal") and after PIT. At 1 and 3 days after PIT, [(18)F]FDG indicated lower uptake in the infarct area. Interestingly, unexpectedly high-[(18)F]FDG uptake was observed in the peri-infarct area surrounding the infarct area at day 7. The high-[(18)F]FDG uptake region completely overlapped with the high-[(11)C](R)-PK uptake region at day 7, which resulted in the underestimation of neuronal damage. Immunohistochemical data also suggested that the high-[(18)F]FDG uptake peak at day 7 was caused by inflammation including microglial cell activation. In contrast, imaging with [(11)C]FMZ indicated cortical neuronal damage on days 7 and 14 without any disturbance by microglial formation. These results indicated that [(18)F]FDG might not be a suitable ligand for ischemic neuronal damage detection from acute to subacute phases.