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 [C-11](R)-PK11195 ([C-11](R)-PK) for peripheral benzodiazepine receptor (PBR), [C-11]flumazenil ([C-11]FMZ) for central benzodiazepine receptor (CBR), and [F-18]fluoro-2-deoxy-D-glucose ([F-18]FDG) for glucose metabolism at before (as "Normal") and after PIT. At 1 and 3 days after PIT, [F-18]FDG indicated lower uptake in the infarct area. Interestingly, unexpectedly high-[F-18]FDG uptake was observed in the peri-infarct area surrounding the infarct area at day 7. The high-[F-18]FDG uptake region completely overlapped with the high-[C-11](R)-PK uptake region at day 7, which resulted in the underestimation of neuronal damage. Immunohistochemical data also suggested that the high-[F-18]FDG uptake peak at day 7 was caused by inflammation including microglial cell activation. In contrast, imaging with [C-11]FMZ indicated cortical neuronal damage on days 7 and 14 without any disturbance by microglial formation. These results indicated that [F-18]FDG might not be a suitable ligand for ischemic neuronal damage detection from acute to subacute phases. Synapse 65:207-214, 2011. (C) 2010 Wiley-Liss, Inc.