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EJNMMI Research
Published in: EJNMMI Research 1/2012

Open Access 01-12-2012 | Original research

PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy

Authors: Stefanie Dedeurwaerdere, Paul D Callaghan, Tien Pham, Gita L Rahardjo, Halima Amhaoul, Paula Berghofer, Mitchell Quinlivan, Filomena Mattner, Christian Loc'h, Andrew Katsifis, Marie-Claude Grégoire

Published in: EJNMMI Research | Issue 1/2012

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Abstract

Background

Recently, inflammatory cascades have been suggested as a target for epilepsy therapy. Positron emission tomography (PET) imaging offers the unique possibility to evaluate brain inflammation longitudinally in a non-invasive translational manner. This study investigated brain inflammation during early epileptogenesis in the post-kainic acid-induced status epilepticus (KASE) model with post-mortem histology and in vivo with [18F]-PBR111 PET.

Methods

Status epilepticus (SE) was induced (N = 13) by low-dose injections of KA, while controls (N = 9) received saline. Translocator protein (TSPO) expression and microglia activation were assessed with [125I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [18F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [18F]-PBR111 volume of distribution (V t) in volume of interests (VOIs) was quantified by means of kinetic modelling and a VOI/metabolite-corrected plasma activity ratio.

Results

Animals with substantial SE showed huge overexpression of TSPO in vitro in relevant brain regions such as the hippocampus and amygdala (P < 0.001), while animals with mild symptoms displayed a smaller increase in TSPO in amygdala only (P < 0.001). TSPO expression was associated with OX-42 signal but without obvious cell loss. Similar in vivo [18F]-PBR111 increases in V t and the simplified ratio were found in key regions such as the hippocampus (P < 0.05) and amygdala (P < 0.01).

Conclusion

Both post-mortem and in vivo methods substantiate that the brain regions important in seizure generation display significant brain inflammation during epileptogenesis in the KASE model. This work enables future longitudinal investigation of the role of brain inflammation during epileptogenesis and evaluation of anti-inflammatory treatments.
Appendix
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Metadata
Title
PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy
Authors
Stefanie Dedeurwaerdere
Paul D Callaghan
Tien Pham
Gita L Rahardjo
Halima Amhaoul
Paula Berghofer
Mitchell Quinlivan
Filomena Mattner
Christian Loc'h
Andrew Katsifis
Marie-Claude Grégoire
Publication date
01-12-2012
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2012
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/2191-219X-2-60

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