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Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers
Author(s) -
Bascuñana Pablo,
Gendron Thibault,
Sander Kerstin,
Jahreis Ina,
Polyak Andras,
Ross Tobias L.,
Bankstahl Marion,
Arstad Erik,
Bankstahl Jens P.
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.16353
Subject(s) - epileptogenesis , translocator protein , status epilepticus , context (archaeology) , epilepsy , neuroinflammation , positron emission tomography , medicine , neuroscience , nuclear medicine , chemistry , psychology , biology , paleontology , inflammation
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; mG luR5), 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.