Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers
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| Názov: | Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers |
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| Autori: | András Polyák, Thibault Gendron, Tobias L. Ross, Erik Årstad, Ina Jahreis, Jens P. Bankstahl, Kerstin Sander, Pablo Bascuñana, Marion Bankstahl |
| Prispievatelia: | KAS - Konrad-Adenauer-Stiftung, EU - European Union |
| Zdroj: | Epilepsia. 60:2325-2333 |
| Informácie o vydavateľovi: | Wiley, 2019. |
| Rok vydania: | 2019 |
| Predmety: | Epilepsy/diagnostic imaging, Epilepsy/metabolism, glutamate receptor, Physique, chimie, mathématiques & sciences de la terre, microglia, Biomarkers/metabolism, Sciences de la santé humaine, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Physical, chemical, mathematical & earth Sciences, Chimie, Animals, Human health sciences, Epilepsy, astroglia, Receptors, GABA-A/metabolism, Receptors, Glutamate/metabolism, GABAA receptor, Radiologie, médecine & imagerie nucléaire, Positron-Emission Tomography/methods, Receptors, GABA-A, Rats, 3. Good health, Chemistry, Neurology, Receptors, Glutamate, Inflammation Mediators/metabolism, Positron-Emission Tomography, epilepsy, Female, Neurology (clinical), Inflammation Mediators, Biomarkers, Radiology, nuclear medicine & imaging |
| Popis: | ObjectiveIdentification 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.MethodsAs 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; 18F‐flumazenil (18F‐FMZ; GABAA receptor), 18F‐FPEB (metabotropic glutamate receptor 5; mGluR5), 18F‐flutriciclamide (translocator protein; TSPO, microglia activation) and 18F‐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/mm2) was calculated.ResultsIn epileptogenesis‐associated brain regions, 18F‐FMZ and 18F‐FPEB showed an early decrease after SE. 18F‐FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18F‐FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18F‐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, 18F‐deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase.SignificanceAutoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter‐related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments. |
| Druh dokumentu: | Article |
| Jazyk: | English |
| ISSN: | 1528-1167 0013-9580 |
| DOI: | 10.1111/epi.16353 |
| Prístupová URL adresa: | https://discovery.ucl.ac.uk/10084215/1/Arstad_AAM_20190828_Pilocarpine%20timeline_revised.pdf https://pubmed.ncbi.nlm.nih.gov/31571210 https://www.ncbi.nlm.nih.gov/pubmed/31571210 https://pubmed.ncbi.nlm.nih.gov/31571210/ https://elib.tiho-hannover.de/receive/tiho_mods_00002021 https://onlinelibrary.wiley.com/doi/full/10.1111/epi.16353 https://discovery-pp.ucl.ac.uk/id/eprint/10084215/ |
| Rights: | Wiley Online Library User Agreement |
| Prístupové číslo: | edsair.doi.dedup.....3265e59708921b2039acbe65a3c7a06c |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | ObjectiveIdentification 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.MethodsAs 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; 18F‐flumazenil (18F‐FMZ; GABAA receptor), 18F‐FPEB (metabotropic glutamate receptor 5; mGluR5), 18F‐flutriciclamide (translocator protein; TSPO, microglia activation) and 18F‐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/mm2) was calculated.ResultsIn epileptogenesis‐associated brain regions, 18F‐FMZ and 18F‐FPEB showed an early decrease after SE. 18F‐FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18F‐FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18F‐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, 18F‐deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase.SignificanceAutoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter‐related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments. |
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| ISSN: | 15281167 00139580 |
| DOI: | 10.1111/epi.16353 |