Mirjam Brackhan1, Pablo Bascuñana2, Johannes M Postema2, Tobias L Ross2, Frank M Bengel2, Marion Bankstahl3, Jens P Bankstahl4. 1. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany. 2. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and. 3. Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany. 4. Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and bankstahl.jens@mh-hannover.de.
Abstract
UNLABELLED: Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. METHODS: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to (11)C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm(3) and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. RESULTS: After SE, increases in (11)C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. CONCLUSION: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.
UNLABELLED: Experimental and clinical evidence suggests that neuroinflammation, triggered by epileptogenic insults, contributes to seizure development. We used translocator protein-targeted molecular imaging to obtain further insights into the role of microglial activation during epileptogenesis. METHODS: As epileptogenic insult, a status epilepticus (SE) was induced in rats by lithium pilocarpine. Rats were subjected to (11)C-PK11195 PET scans before SE; at 4 h after SE; at 1, 2, 5, 7, 14, and 22 d after SE; and at 14-16 wk after SE. For data evaluation, brain regions were outlined by coregistration with a standard rat brain atlas, and percentage injected dose/cm(3) and binding potential (simplified reference tissue model with cerebellar gray matter as a reference region) were calculated. For autoradiography and immunohistochemical evaluation, additional rats were decapitated without prior SE or 2, 5, or 14 d after SE. RESULTS: After SE, increases in (11)C-PK11195 uptake and binding potential were evident in epileptogenesis-associated brain regions, such as the hippocampus, thalamus, or piriform cortex, but not in the cerebellum beginning at 2-5 d and persisting at least 3 wk after SE. Maximal regional signal was observed at 1-2 wk after SE. Autoradiography confirmed the spatiotemporal profile. Immunohistochemical evaluation revealed microglial and astroglial activation as well as neuronal cell loss in epileptogenesis-associated brain regions at all investigated time points. The time course of microglial activation was consistent with that demonstrated by tracer techniques. CONCLUSION: Translocator protein-targeted PET is a reliable tool for identifying brain inflammation during epileptogenesis. Neuroinflammation mainly affects brain regions commonly associated with seizure generation and spread. Definition of the time profile of neuroinflammation may facilitate the development of inflammation-targeted, antiepileptogenic therapy.
Authors: Leah P Dickstein; Jeih-San Liow; Alison Austermuehle; Sami Zoghbi; Sara K Inati; Kareem Zaghloul; Paolo Zanotti-Fregonara; William H Theodore Journal: Epilepsia Date: 2019-05-30 Impact factor: 5.864
Authors: Brad A Hobson; Douglas J Rowland; Sílvia Sisó; Michelle A Guignet; Zachary T Harmany; Suren B Bandara; Naomi Saito; Danielle J Harvey; Donald A Bruun; Joel R Garbow; Abhijit J Chaudhari; Pamela J Lein Journal: Toxicol Sci Date: 2019-08-01 Impact factor: 4.849
Authors: Pablo Bascuñana; Mirjam Brackhan; Ina Leiter; Heike Keller; Ina Jahreis; Tobias L Ross; Frank M Bengel; Marion Bankstahl; Jens P Bankstahl Journal: J Cereb Blood Flow Metab Date: 2018-10-30 Impact factor: 6.200
Authors: Vera Russmann; Matthias Brendel; Erik Mille; Angela Helm-Vicidomini; Roswitha Beck; Lisa Günther; Simon Lindner; Axel Rominger; Michael Keck; Josephine D Salvamoser; Nathalie L Albert; Peter Bartenstein; Heidrun Potschka Journal: Neuroimage Clin Date: 2017-04-05 Impact factor: 4.881
Authors: Marion Bankstahl; Heike Breuer; Ina Leiter; Martin Märkel; Pablo Bascuñana; Dominik Michalski; Frank M Bengel; Wolfgang Löscher; Martin Meier; Jens P Bankstahl; Wolfgang Härtig Journal: eNeuro Date: 2018-05-30
Authors: S K Vainio; A M Dickens; J Tuisku; O Eskola; O Solin; E Löyttyniemi; D C Anthony; J O Rinne; L Airas; M Haaparanta-Solin Journal: EJNMMI Res Date: 2019-05-09 Impact factor: 3.138