Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers.

Autor: Bascuñana P; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany., Gendron T; Institute of Nuclear Medicine, University College London, London, UK.; Department of Chemistry, University College London, London, UK., Sander K; Institute of Nuclear Medicine, University College London, London, UK.; Department of Chemistry, University College London, London, UK., Jahreis I; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.; Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany., Polyak A; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany., Ross TL; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany., Bankstahl M; Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.; Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany., Arstad E; Institute of Nuclear Medicine, University College London, London, UK.; Department of Chemistry, University College London, London, UK., Bankstahl JP; Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Jazyk: angličtina
Zdroj: Epilepsia [Epilepsia] 2019 Nov; Vol. 60 (11), pp. 2325-2333. Date of Electronic Publication: 2019 Oct 01.
DOI: 10.1111/epi.16353
Abstrakt: Objective: Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease.
Methods: As development of novel radiotracers and on-site setup of existing radiotracers is highly time-consuming and expensive, we used dual-centre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18 F-flumazenil ( 18 F-FMZ; GABA A receptor), 18 F-FPEB (metabotropic glutamate receptor 5; mGluR5), 18 F-flutriciclamide (translocator protein; TSPO, microglia activation) and 18 F-deprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpine-induced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12-14 weeks after SE) were normalized to a calibration curve, co-registered to an MRI-based 2D region-of-interest atlas, and activity concentration (Bq/mm 2 ) was calculated.
Results: In epileptogenesis-associated brain regions, 18 F-FMZ and 18 F-FPEB showed an early decrease after SE. 18 F-FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18 F-FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18 F-flutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5-15 days and decreasing during the chronic phase. On the other hand, 18 F-deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase.
Significance: Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter-related targets like glutamate and GABA A receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments.
(Wiley Periodicals, Inc. © 2019 International League Against Epilepsy.)
Databáze: MEDLINE
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