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

  • Dedeurwaerdere S
  • Callaghan P
  • Pham T
 et al. 
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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 [ 18 F]-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 [ 125 I]-CLINDE autoradiography and OX-42 immunohistochemistry, respectively, 7 days post-SE. In a subgroup of rats, [ 18 F]-PBR111 PET imaging with metabolite-corrected input function was performed before post-mortem evaluation. [ 18 F]-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 [ 18 F]-PBR111 increases in Vt 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. © 2012 Dedeurwaerdere et al.

Author-supplied keywords

  • Neuroinflammation
  • Rat
  • Status epilepticus
  • Temporal lobe epilepsy
  • [ F]-PBR111 18

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Authors

  • S. Dedeurwaerdere

  • P.D. Callaghan

  • T. Pham

  • G.L. Rahardjo

  • H. Amhaoul

  • P. Berghofer

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