title: Serial Quantitative TSPO-Targeted PET Reveals Peak Microglial Activation up to 2 Weeks After an Epileptogenic Brain Insult.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Brackhan
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and.
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Postema
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and.
authors.forename: Tobias L
authors.initials: TL
authors.lastname: Ross
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and.
authors.forename: Frank M
authors.initials: FM
authors.lastname: Bengel
authors.affiliation: Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine, Hannover, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Bankstahl
authors.affiliation: Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany; and bankstahl.jens@mh-hannover.de.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Bankstahl
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004827:Epilepsy / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D007546:Isoquinolines / Q000493:pharmacokinetics*; D017628:Microglia / Q000378:metabolism*; D057089:Pathology, Molecular / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D007546:Isoquinolines; D019275:Radiopharmaceuticals; D018079:Receptors, GABA; C499229:TSPO protein, human; C037850:PK 11195
keywords: PET; TSPO; brain inflammation; epileptogenesis; microglia activation