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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24166

Title: Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities
Authors: Bertoglio, Daniele
Verhaeghe, Jeroen
Santermans, Eva
Amhaoul, Halima
Jonckers, Elisabeth
Wyffels, Leonie
Van Der Linden, Annemie
Hens, Niel
Staelens, Steven
Dedeurwaerdere, Stefanie
Issue Date: 2017
Citation: BRAIN BEHAVIOR AND IMMUNITY, 61, p. 69-79
Abstract: Brain inflammation is an important factor in the conversion of a healthy brain into an epileptic one, a phenomenon known as epileptogenesis, offering a new entry point for prognostic tools. The development of anti-epileptogenic therapies to treat before or at disease onset is hampered by our inability to predict the severity of the disease outcome. In a rat model of temporal lobe epilepsy we aimed to assess whether in vivo non-invasive imaging of brain inflammation at disease onset was predictive of spontaneous recurrent seizures (SRS) frequency and severity of depression-like and sensorimotor-related comorbidities. To this end, translocator protein, a biomarker of inflammation, was imaged by means of positron emission tomography (PET) 2 and 4 weeks post-status epilepticus using [F-18]-PBR111. Translocator protein was highly upregulated 2 weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, P < 0.001), whereas 4 weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, P < 0.01) and was only apparent in a subset of these regions. Animals were monitored with video-electroencephalography during all stages of disease (acute, latent-first seizures appearing around 2 weeks post-status epilepticus-and chronic phases), for a total of 12 weeks, in order to determine SRS frequency for each subject (range 0.00-0.83 SRS/day). We found that regional PET uptake at 2 and 4 weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (P < 0.05 for each test). Regional PET imaging did not correlate with SRS frequency, however, by applying a multivariate data-driven modeling approach based on translocator protein PET imaging at 2 weeks post-status epilepticus, we accurately predicted the frequency of SRS (R = 0.92; R-2 = 0.86; P < 0.0001) at the onset of epilepsy. This study not only demonstrates non-invasive imaging of translocator protein as a prognostic biomarker to ascertain SRS frequency, but also shows its capability to reflect the severity of depression-like and sensorimotor-related comorbidities. Our results are an encouraging step towards the development of anti-epileptogenic treatments by providing early quantitative assessment of SRS frequency and severity of comorbidities with high clinical relevance.(C) 2016 Elsevier Inc. All rights reserved.
Notes: [Bertoglio, Daniele; Dedeurwaerdere, Stefanie] Univ Antwerp, Dept Translat Neurosci, Antwerp, Belgium. [Verhaeghe, Jeroen; Wyffels, Leonie; Staelens, Steven] Univ Antwerp, Mol Imaging Ctr Antwerp, Antwerp, Belgium. [Santermans, Eva; Hens, Niel] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Diepenbeek, Belgium. [Jonckers, Elisabeth; Van Der Linden, Annemie] Univ Antwerp, Bioimaging Lab, Antwerp, Belgium. [Wyffels, Leonie] Univ Antwerp Hosp, Dept Nucl Med, Edegem, Belgium. [Hens, Niel] Univ Antwerp, Vaccine & Infect Dis Inst, Ctr Hlth Econ Res & Modelling Infect Dis, Antwerp, Belgium.
URI: http://hdl.handle.net/1942/24166
DOI: 10.1016/j.bbi.2016.12.015
ISI #: 000395365900010
ISSN: 0889-1591
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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