Article

Increased In Vivo Expression of an Inflammatory Marker in Temporal Lobe Epilepsy

Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1026, USA.
Journal of Nuclear Medicine (Impact Factor: 6.16). 02/2012; 53(2):234-40. DOI: 10.2967/jnumed.111.091694
Source: PubMed

ABSTRACT

Animal studies and clinical observations suggest that epilepsy is associated with inflammation. Translocator protein (TSPO) (18 kDa), a marker of inflammation, is increased in vitro in surgical samples from patients with temporal lobe epilepsy. TSPO can be measured in the living human brain with PET and the novel radioligand (11)C-PBR28. In this study, we sought to determine whether in vivo expression of TSPO is increased ipsilateral to the seizure focus in patients with temporal lobe epilepsy.
Sixteen patients with unilateral temporal lobe epilepsy and 30 healthy subjects were studied with (11)C-PBR28 PET and MRI. Uptake of radioactivity after injection of (11)C-PBR28 was measured from regions of interest drawn bilaterally onto MR images. Brain uptake from ipsilateral and contralateral hemispheres was compared using a paired-samples t test.
We found that brain uptake was higher ipsilateral to the seizure focus in the hippocampus, parahippocampal gyrus, amygdala, fusiform gyrus, and choroid plexus but not in other brain regions. This asymmetry was more pronounced in patients with hippocampal sclerosis than in those without.
We found increased uptake of radioactivity after injection of (11)C-PBR28 ipsilateral to the seizure focus in patients with temporal lobe epilepsy, suggesting increased expression of TSPO. Studies in larger samples are required to confirm this finding and determine the clinical utility of imaging TSPO in temporal lobe epilepsy.

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    • "Positron emission tomography (PET) has been used in an attempt to image activation of astrocytes and microglial/macrophages in vivo using radioligands for the detection of the translocator protein (TSPO) (18 kDa, a marker of neuroinflammation) (Chen and Guilarte 2008;Cosenza-Nashat et al. 2009). A recent study reported an increased uptake of radioactivity after injection of 11C-PBR28 (a new tracer for the detection of TSPO) ipsilateral to the seizure focus (within the hippocampus) of TLE patients, particularly in patients with HS (Hirvonen et al. 2012). Additional studies are, however , needed to determine the clinical utility of imaging TSPO, and to correlate increases in TSPO binding with the neuropathological finding in patients undergoing epilepsy surgery. "
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    ABSTRACT: This review reports the available evidence on the activation of the innate and adaptive branches of the immune system and the related inflammatory processes in epileptic disorders and the putative pathogenic role of inflammatory processes developing in the brain, as indicated by evidence from experimental and clinical research. Indeed, there is increasing knowledge supporting a role of specific inflammatory mediators and immune cells in the generation and recurrence of epileptic seizures, as well as in the associated neuropathology and comorbidities. Major challenges in this field remain: a better understanding of the key inflammatory pathogenic pathways activated in chronic epilepsy and during epileptogenesis, and how to counteract them efficiently without altering the homeostatic tissue repair function of inflammation. The relevance of this information for developing novel therapies will be highlighted.
    Full-text · Article · Dec 2015 · Cold Spring Harbor Perspectives in Medicine
    • "In TLE patients, an induction of TSPO expression has been confirmed in surgical specimen (Sauvageau et al., 2002). In line with these findings, Hirvonen et al. (2012) described increased uptake of the TSPO ligand [ 11 C]-PBR28 in the seizure focus of TLE patients. Recently, first data from an experimental post-status epilepticus model have been reported (Dedeurwaerdere et al., 2012). "
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    ABSTRACT: Neuroinflammation has been suggested as a key determinant of the intrinsic severity of epilepsy. Glial cell activation and associated inflammatory signaling can influence seizure thresholds as well as the pharmacodynamics and pharmacokinetics of antiepileptic drugs. Based on these data, we hypothesized that molecular imaging of microglia activation might serve as a tool to predict drug refractoriness of epilepsy. Brain uptake of (R)-[11C]PK11195, a ligand of the translocator protein 18 kDa and molecular marker of microglia activation, was studied in a chronic model of temporal lobe epilepsy in rats with selection of phenobarbital responders and non-responders. In rats with drug-sensitive epilepsy, (R)-[11C]PK11195 brain uptake values were comparable to those in non-epileptic controls. Analysis in non-responders revealed enhanced brain uptake of up to 39% in different brain regions. The difference might be related to the fact that non-responders exhibited higher baseline seizure frequencies than responders indicating a more pronounced intrinsic disease severity. In hippocampal sections, ED1 immunostaining argued against a general difference in microglia activation between both groups. Our data suggest that TSPO PET imaging might serve as a biomarker for drug resistance in temporal lobe epilepsy. However, it needs to be considered that our findings indicate that the TSPO PET data might merely reflect seizure frequency. Future experimental and clinical studies should further evaluate the validity of TSPO PET data to predict the response to phenobarbital and other antiepileptic drugs in longitudinal studies with scanning before drug exposure and with a focus on the early phase following an epileptogenic brain insult.
    No preview · Article · Oct 2014 · Neuropharmacology
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    • "Positron emission tomography (PET) scanning with a number of ligands has been used to quantitate TSPO expression [8]. We recently developed and validated the utility of a new ligand, 11C-PBR28 that has higher sensitivity to detect increases in TSPO compared to the first generation of ligand, 11C-PK 11195 [9,10,11]. "
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