Positron emission tomography with 11C-flumazenil in the rat shows preservation of binding sites during the acute phase after 2h-transient focal ischemia

Background and purpose: Positron emission tomography (PET) studies in humans have used 11C-flumazenil (FMZ) to assess neuronal viability after stroke. Here we aimed to study whether 11C-FMZ binding was sensitive to neuronal damage in the acute phase following ischemia/reperfusion in the rat brain. Experimental procedures: Transient (2 h followed by reperfusion) and permanent intraluminal middle cerebral artery occlusion was carried out. 11C-FMZ binding was studied by PET up to 24 h after the onset of ischemia. Tissue infarction was evaluated post-mortem at 24 h. Immunohistochemistry against a neuronal nuclei specific protein (NeuN) was performed to assess neuronal injury. Results: No decrease in 11C-FMZ binding was detected in the ipsilateral cortex up to 24 h post-ischemia in the model of transient occlusion despite the fact that rats developed cortical and striatal infarction, and neuronal injury was clearly apparent at this time. In contrast, 11C-FMZ binding was significantly depressed in the ipsilateral cortex at 24 h following permanent ischemia. Conclusions: This finding evidences that 11C-FMZ binding is not sensitive to neuronal damage on the acute phase of ischemia/reperfusion in the rat brain.

▶We used PET with 11C-flumazenil to evaluate brain ischemia in rats. ▶11C-flumazenil is not sensitive to neuronal death in transient cerebral ischemia. ▶11C-flumazenil binding was clearly altered in animals subjected to permanent ischemia. ▶With reperfusion, 11C-flumazenil bound even in the pannecrotic infracted brain. ▶Our results contrast with previous published descriptive studies in humans.