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Neurobiol Dis. 2015 Oct;82:526-539. doi: 10.1016/j.nbd.2015.09.004. Epub 2015 Sep 24.

Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis.

Author information

1
Department of Translational Neurosciences, University of Antwerp, Belgium.
2
Department of Translational Neurosciences, University of Antwerp, Belgium; Bio-Imaging Lab, University of Antwerp, Belgium.
3
Molecular Imaging Center Antwerp, University of Antwerp, Belgium.
4
Laboratory of Neurochemistry and Behaviour, University of Antwerp, Belgium.
5
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.
6
Laboratory of Cell Biology & Histology, University of Antwerp, Belgium.
7
Department of PET and Nuclear Medicine, Royal Prince Alfred Hospital, Australia.
8
Bio-Imaging Lab, University of Antwerp, Belgium.
9
Department of Translational Neurosciences, University of Antwerp, Belgium. Electronic address: stefanie.dedeurwaerdere@uantwerpen.be.

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.

KEYWORDS:

(18)F-PBR111 PET; Brain- and neuroinflammation; Epilepsy; Microglia; Seizure; Translocator protein or peripheral benzodiazepine receptor

PMID:
26388398
DOI:
10.1016/j.nbd.2015.09.004
[Indexed for MEDLINE]

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