TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

• Published in: NeuroImage clinical 2021-01, Vol.31, p.102701-102701, Article 102701
• Main Authors: Bertoglio, Daniele, Amhaoul, Halima, Goossens, Joery, Ali, Idrish, Jonckers, Elisabeth, Bijnens, Tom, Siano, Matteo, wyffels, Leonie, Verhaeghe, Jeroen, Van der Linden, Annemie, Staelens, Steven, Dedeurwaerdere, Stefanie
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Carrier Proteins - metabolism; Disease Models, Animal; Epilepsy, Temporal Lobe - diagnostic imaging; Epilepsy, Temporal Lobe - metabolism; Inflammation; Kainic acid; KASE; Molecular Imaging; Neuroimaging; PET imaging; Phenotype; Positron-Emission Tomography; Rats; Receptors, GABA-A - metabolism; Regular; Translocator protein; Up-Regulation
• ISSN: 2213-1582; 2213-1582
• DOI: 10.1016/j.nicl.2021.102701

[Display omitted] •Translocator protein (TSPO) PET imaging identifies different epileptic categories.•TSPO levels at disease onset and chronic disease are unrelated in KASE rats.•TSPO expression changes dynamically during epilepsy.•Histopathology during chronic epilepsy is associated to TSPO levels.•TSPO upregulation during disease progression may be based on two superimposed processes. Neuroinflammation is a key component of epileptogenesis, the process leading to acquired epilepsy. In recent years, with the development of non-invasive in vivo positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO), a marker of neuroinflammation, it has become possible to perform longitudinal studies to characterize neuroinflammation at different disease stages in animal models of epileptogenesis. This study aimed to utilize the prognostic capability of TSPO PET imaging at disease onset (2 weeks post-SE) to categorize epileptic rats with distinct seizure burden based on TSPO levels at disease onset and investigate their association to TSPO expression at the chronic epilepsy stage. Controls (n = 14) and kainic acid-induced status epilepticus (KASE) rats (n = 41) were scanned non-invasively with [18F]PBR111 PET imaging measuring TSPO expression. Animals were monitored using video-electroencephalography (vEEG) up to chronic disease (12 weeks post-SE), at which TSPO levels ([3H]PK11195) as well as other post-mortem abnormalities (namely synaptic density ([3H]UCB-J), neuronal loss (NeuN), and neurodegeneration (FjC)) were investigated. By applying multivariate analysis, TSPO PET imaging at disease onset identified three KASE groups with significantly different spontaneous recurrent seizures (SRS) burden (defined as rare SRS, sporadic SRS, and frequent SRS) (p = 0.003). Interestingly, TSPO levels were significantly different when comparing the three KASE groups (p