title: Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis.
abstract: OBJECTIVE
  A hallmark in the neuropathology of temporal lobe epilepsy is brain inflammation which has been suggested as both a biomarker and a new mechanistic target for treatments. The translocator protein (TSPO), due to its high upregulation under neuroinflammatory conditions and the availability of selective PET tracers, is a candidate target. An important step to exploit this target is a thorough characterisation of the spatiotemporal profile of TSPO during epileptogenesis.
  
  
  METHODS
  TSPO expression, microglial activation, astrocyte reactivity and cell loss in several brain regions were evaluated at five time points during epileptogenesis, including the chronic epilepsy phase in the kainic acid-induced status epilepticus (KASE) model (n = 52) and control Wistar Han rats (n = 33). Seizure burden was also determined in the chronic phase. Furthermore, ¹⁸F-PBR111 PET/MRI scans were acquired longitudinally in an additional four KASE animals.
  
  
  RESULTS
  TSPO expression measured with in vitro and in vivo techniques was significantly increased at each time point and peaked two weeks post-SE in the limbic system. A prominent association between TSPO expression and activated microglia (p < 0.001; r = 0.7), as well as cell loss (p < 0.001; r = -0.8) could be demonstrated. There was a significant positive correlation between spontaneous seizures and TSPO upregulation in several brain regions with increased TSPO expression.
  
  
  CONCLUSIONS
  TSPO expression was dynamically upregulated during epileptogenesis, persisted in the chronic phase and correlated with microglia activation rather than reactive astrocytes. TSPO expression was correlating with spontaneous seizures and its high expression during the latent phase might possibly suggest being an important switching point in disease ontogenesis which could be further investigated by PET imaging.
authors.affiliation: Department of Translational Neurosciences, University of Antwerp, Belgium.
authors.forename: Halima
authors.initials: H
authors.lastname: Amhaoul
authors.affiliation: Department of Translational Neurosciences, University of Antwerp, Belgium; Bio-Imaging Lab, University of Antwerp, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Hamaide
authors.affiliation: Department of Translational Neurosciences, University of Antwerp, Belgium.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bertoglio
authors.affiliation: Department of Translational Neurosciences, University of Antwerp, Belgium.
authors.forename: Stephanie Nadine
authors.initials: SN
authors.lastname: Reichel
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: Laboratory of Neurochemistry and Behaviour, University of Antwerp, Belgium.
authors.forename: Elly
authors.initials: E
authors.lastname: Geerts
authors.affiliation: Laboratory of Neurochemistry and Behaviour, University of Antwerp, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Van Dam
authors.affiliation: Laboratory of Neurochemistry and Behaviour, University of Antwerp, Belgium; Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Belgium; Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen (UMCG), The Netherlands.
authors.forename: Peter Paul
authors.initials: PP
authors.lastname: De Deyn
authors.affiliation: Laboratory of Cell Biology & Histology, University of Antwerp, Belgium.
authors.forename: Samir
authors.initials: S
authors.lastname: Kumar-Singh
authors.affiliation: Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
authors.affiliation: Bio-Imaging Lab, University of Antwerp, Belgium.
authors.forename: Annemie
authors.initials: A
authors.lastname: Van Der Linden
authors.affiliation: Molecular Imaging Center Antwerp, University of Antwerp, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Staelens
authors.affiliation: Department of Translational Neurosciences, University of Antwerp, Belgium. Electronic address: stefanie.dedeurwaerdere@uantwerpen.be.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dedeurwaerdere
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000378:metabolism*; D002908:Chronic Disease; D004195:Disease Models, Animal; D018450:Disease Progression; D000069280:Electrocorticography; D004660:Encephalitis / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D004827:Epilepsy / Q000000981:diagnostic imaging / Q000276:immunology* / Q000473:pathology; D005500:Follow-Up Studies; D007150:Immunohistochemistry; D007608:Kainic Acid; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D009457:Neuroglia / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D009474:Neurons / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology; D049268:Positron-Emission Tomography; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D007608:Kainic Acid
keywords: (18)F-PBR111 PET; Brain- and neuroinflammation; Epilepsy; Microglia; Seizure; Translocator protein or peripheral benzodiazepine receptor