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Title
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Non-invasive PET imaging of brain inflammation at disease onset predicts spontaneous recurrent seizures and reflects comorbidities
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Brain, behavior, and immunity. - San Diego, Calif.
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Publication
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San Diego, Calif.
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2017
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ISSN
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0889-1591
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DOI
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10.1016/J.BBI.2016.12.015
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Volume/pages
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61
(2017)
, p. 69-79
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ISI
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000395365900010
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Pubmed ID
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28017648
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Full text (Publisher's DOI)
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Full text (open access)
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Full text (publisher's version - intranet only)
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