Divergent metabolic substrate utilization in brain during epileptogenesis precedes chronic hypometabolism.

Alterations in metabolism during epileptogenesis may be a therapy target. Recently, an increase in amino acid transport into the brain was proposed to play a role in epileptogenesis. We aimed to characterize alterations of substrate utilization during epileptogenesis and in chronic epilepsy. The lithium-pilocarpine post status epilepticus (SE) rat model was used. We performed longitudinal O-(2-[(18)F]fluoroethyl)-l-tyrosine (F-18-FET) and F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) and calculated F-18-FET volume of distribution (V-t) and F-18-FDG uptake. Correlation analyses were performed with translocator protein-PET defined neuroinflammation from previously acquired data. We found reduced F-18-FET V-t at 48 h after SE (amygdala: -30.2%, p = 0.014), whereas F-18-FDG showed increased glucose uptake 4 and 24 h after SE (hippocampus: + 43.6% and +42.5%, respectively; p < 0.001) returning to baseline levels thereafter. In chronic epileptic animals, we found a reduction in F-18-FET and F-18-FDG in the hippocampus. No correlation was found for F-18-FET or F-18-FDG to microglial activation at seven days post SE. Whereas metabolic alterations do not reflect higher metabolism associated to activated microglia, they might be partially driven by chronic neuronal loss. However, both metabolisms diverge during early epileptogenesis, pointing to amino acid turnover as a possible biomarker and/or therapeutic target for epileptogenesis.