کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5040690 | 1473906 | 2017 | 11 صفحه PDF | دانلود رایگان |
- KASE rats display depression-like and sensorimotor-related comorbidities.
- Translocator protein PET imaging correlates severity of investigated comorbidities.
- Translocator protein PET imaging predicts spontaneous seizure frequency.
- Non-invasive PET imaging is a prognostic biomarker for seizure frequency.
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 4Â weeks post-status epilepticus using [18F]-PBR111. Translocator protein was highly upregulated 2Â weeks post-status epilepticus in limbic structures (up to 2.1-fold increase compared to controls in temporal lobe, PÂ <Â 0.001), whereas 4Â weeks post-status epilepticus, upregulation decreased (up to 1.6-fold increase compared to controls in temporal lobe, PÂ <Â 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 2Â weeks post-status epilepticus - and chronic phases), for a total of 12Â weeks, in order to determine SRS frequency for each subject (range 0.00-0.83Â SRS/day). We found that regional PET uptake at 2 and 4Â weeks post-status epilepticus correlated with the severity of depression-like and sensorimotor-related comorbidities during chronic epilepsy (PÂ <Â 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 2Â weeks post-status epilepticus, we accurately predicted the frequency of SRS (RÂ =Â 0.92; R2Â =Â 0.86; PÂ <Â 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.
Journal: Brain, Behavior, and Immunity - Volume 61, March 2017, Pages 69-79