Title
Brain inflammation in a chronic epilepsy model : evolving pattern of the translocator protein during epileptogenesisBrain inflammation in a chronic epilepsy model : evolving pattern of the translocator protein during epileptogenesis
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Research group
Translational Neurosciences (TNW)
Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO)
Bio-Imaging lab
Laboratory of cell biology and histology
Neurochemistry and behaviour
Publication type
article
Publication
San Diego, Calif.,
Subject
Human medicine
Source (journal)
Neurobiology of disease. - San Diego, Calif.
Volume/pages
82(2015), p. 526-539
ISSN
0969-9961
ISI
000364980000050
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/4e4cc7/128314.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/910731/128314.pdf
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