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

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

SUBMITTER: Bascunana P

PROVIDER: S-EPMC6928550 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Bascuñana Pablo P Brackhan Mirjam M Leiter Ina I Keller Heike H Jahreis Ina I Ross Tobias L TL Bengel Frank M FM Bankstahl Marion M Bankstahl Jens P JP

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20181030 1

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 (18F-FET) and 18F-fluorodeoxyglucose (18</sup ...[more]

PMID: 30375913

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

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

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