Longitudinal microPET imaging of brain glucose metabolism in rat lithium-pilocarpine model of epilepsy

Abstract

The lithium-pilocarpine model of epilepsy in rat has been used extensively to investigate basic mechanisms of epilepsy and mimics human temporal lobe epilepsy. Our aim was to investigate longitudinal alterations in metabolism after lithium-pilocarpine induced status epilepticus (SE) using [(18)F]FDG microPET. Twenty-eight Wistar rats received lithium chloride followed by pilocarpine (n=19) or saline (n=9) IP. Continuous video-EEG was used to monitor SE and occurrence of spontaneous seizures (SS). FDG microPET imaging was performed at baseline, on day 3 after drug administration (D3), and at the end of the monitoring period (CR). MicroPET images were spatially normalized to Paxinos space and parametric standardized uptake value (SUV)-images were generated. Metabolism was compared between groups of animals and between different time points. Eighteen animals developed SE, 11 had died by D3. SS were recorded in 3 of 7 surviving SE animals. On D3, metabolism was reduced in SE group compared to controls throughout the brain (-49+/-27%), except for the cerebellum: mostly in hippocampus, entorhinal cortex and thalamus bilaterally. Metabolism tended to be different between SS and no SS animals on D3 in striatum and hippocampus. In CR condition, relative metabolism was significantly different in SE group compared to controls in cerebellum and brainstem bilaterally and left striatum and entorhinal cortex. There were no significant differences between SS and no SS animals in CR condition. Pilocarpine-induced SE causes a severe, but transient reduction in overall metabolism on D3 in rat brain. Metabolic differences on D3 between SS and no SS animals need further study to investigate potential use as an early marker of epileptogenesis.