Increased In Vivo Expression of an Inflammatory Marker in Temporal Lobe Epilepsy
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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ABSTRACT: One compelling challenge in the therapy of epilepsy is to develop anti-epileptogenic drugs with an impact on the disease progression. The search for novel targets has focused recently on brain inflammation since this phenomenon appears to be an integral part of the diseased hyperexcitable brain tissue from which spontaneous and recurrent seizures originate. Although the contribution of specific proinflammatory pathways to the mechanism of ictogenesis in epileptic tissue has been demonstrated in experimental models, the role of these pathways in epileptogenesis is still under evaluation. We review the evidence conceptually supporting the involvement of brain inflammation and the associated blood-brain barrier damage in epileptogenesis, and describe the available pharmacological evidence where post-injury intervention with anti-inflammatory drugs has been attempted. Our review will focus on three main inflammatory pathways, namely the IL-1 receptor/Toll-like receptor signaling, COX-2 and the TGF-β signaling. The mechanisms underlying neuronal-glia network dysfunctions induced by brain inflammation are also discussed, highlighting novel neuromodulatory effects of classical inflammatory mediators such as cytokines and prostaglandins. The increase in knowledge about a role of inflammation in disease progression, may prompt the use of specific anti-inflammatory drugs for developing disease-modifying treatments. This article is part of a Special issue entitled 'Epilepsy'.Neuropharmacology 04/2012; 69. DOI:10.1016/j.neuropharm.2012.04.004 · 4.82 Impact Factor
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ABSTRACT: Over the past decade, an increasing number of observations indicate that activation of inflammatory processes occurs in variety of focal epilepsies. Understanding the feature and consequences of neuroinflammation, including the contribution to development and perpetuation of seizures, as well as to mood or cognitive dysfunction, is a major requisite for delineating its role in epilepsy. The present article discusses the most recent observations supporting the involvement of the inflammatory response in human focal epilepsy. It also evaluates emerging evidence concerning the possibility to identify epilepsy-associated inflammatory biomarkers in cerebrospinal fluid and serum, as well as the potential application of neuroimaging approaches to study the inflammatory reactions in chronic epilepsy patients in vivo, aiming to improve the recognition of appropriate patient populations who might benefit from antiinflammatory or immunomodulatory therapies.Epilepsia 05/2011; 52 Suppl 3:26-32. DOI:10.1111/j.1528-1167.2011.03033.x · 4.58 Impact Factor
Article: Epilepsy and brain inflammation[Show abstract] [Hide abstract]
ABSTRACT: During the last decade, experimental research has demonstrated a prominent role of glial cells, activated in brain by various injuries, in the mechanisms of seizure precipitation and recurrence. In particular, alterations in the phenotype and function of activated astrocytes and microglial cells have been described in experimental and human epileptic tissue, including modifications in potassium and water channels, alterations of glutamine/glutamate cycle, changes in glutamate receptor expression and transporters, release of neuromodulatory molecules (e.g. gliotransmitters, neurotrophic factors), and induction of molecules involved in inflammatory processes (e.g. cytokines, chemokines, prostaglandins, complement factors, cell adhesion molecules) (Seifert et al., 2006; Vezzani et al., 2011; Wetherington et al., 2008). In particular, brain injury or proconvulsant events can activate microglia and astrocytes to release a number of proinflammatory mediators, thus initiating a cascade of inflammatory processes in brain tissue. Proinflammatory molecules can alter neuronal excitability and affect the physiological functions of glia by paracrine or autocrine actions, thus perturbing the glioneuronal communications. In experimental models, these changes contribute to decreasing the threshold to seizures and may compromise neuronal survival (Riazi et al., 2010; Vezzani et al., 2008). In this context, understanding which are the soluble mediators and the molecular mechanisms crucially involved in glio–neuronal interactions is instrumental to shed light on how brain inflammation may contribute to neuronal hyperexcitability in epilepsy.Experimental Neurology 10/2011; 244. DOI:10.1016/j.expneurol.2011.09.033 · 4.62 Impact Factor