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 | Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | Source: | 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. | Keywords: | Epileptogenesis; Translocator protein; PET; Biomarker; Comorbidity; Spontaneous recurrent seizures;Epileptogenesis; Translocator protein; PET; Biomarker; Comorbidity; Spontaneous recurrent seizures | Document URI: | http://hdl.handle.net/1942/24166 | ISSN: | 0889-1591 | e-ISSN: | 1090-2139 | DOI: | 10.1016/j.bbi.2016.12.015 | ISI #: | 000395365900010 | Rights: | © 2016 Elsevier Inc. All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2018 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
bertoglio 1.pdf Restricted Access | Published version | 1.19 MB | Adobe PDF | View/Open Request a copy |
Manuscript_with_figures.pdf | Peer-reviewed author version | 544.44 kB | Adobe PDF | View/Open |
SCOPUSTM
Citations
20
checked on Sep 3, 2020
WEB OF SCIENCETM
Citations
29
checked on Apr 22, 2024
Page view(s)
52
checked on Sep 7, 2022
Download(s)
48
checked on Sep 7, 2022
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.