Publication
Title
Brain inflammation in a chronic epilepsy model : evolving pattern of the translocator protein during epileptogenesis
Author
Abstract
Aims 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.
Language
English
Source (journal)
Neurobiology of disease. - San Diego, Calif.
Publication
San Diego, Calif. : 2015
ISSN
0969-9961
Volume/pages
82(2015), p. 526-539
ISI
000364980000050
Full text (Publisher's DOI)
Full text (open access)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
[E?say:metaLocaldata.cgzprojectinf]
An integrated approach towards understanding the pathogenesis of neurodegeneration (NEUROBRAINNET).
Imaging of Neuroinflammation in Neurodegenerative Diseases (INMIND).
Translocator protein expression in acquired models of epilepsy: picturing a Janus face?
Characterisation of neuroinflammation in an epilepsy model by means of longitudinal in vivo PET/MRI imaging.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 26.10.2015
Last edited 21.11.2017
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