Divergent metabolic substrate utilization in brain during epileptogenesis precedes chronic hypometabolism. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Bascuñana, Pablo; Brackhan, Mirjam; Leiter, Ina; Keller, Heike; Jahreis, Ina; Ross, Tobias L; Bengel, Frank M; Bankstahl, Marion; Bankstahl, Jens P
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 40:Issue 1(2020)
• Page Start: 204
• Page End: 213
• Publication Date: 2020-01
• Subjects: Amino acid turnover -- epilepsy -- fluorodeoxyglucose -- fluoroethyl-l-tyrosine -- positron emission tomography; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X18809886
• Languages: English
• ISSNs: 0271-678X

Abstract

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 ( 18 F-FET) and 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) and calculated 18 F-FET volume of distribution (Vt ) and 18 F-FDG uptake. Correlation analyses were performed with translocator protein-PET defined neuroinflammation from previously acquired data. We found reduced 18 F-FET Vt at 48 h after SE (amygdala: −30.2%, p = 0.014), whereas 18 F-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 18 F-FET and 18 F-FDG in the hippocampus. No correlation was found for 18 F-FET or 18 F-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.