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Abstract

Increased binding sites for "peripheral-type" benzodiazepine receptor (PTBR) ligands have been described in a wide range of neurological disorders including both human and exper-imental epilepsy. This study was undertaken to assess PTBR expression in relation to the presence of hippocampal sclerosis in human temporal lobe epilepsy (TLE). For this pur-pose, hippocampal CA1 subfields were dissected from surgical samples from patients with therapy-refractive TLE with (n D 5) or without (n D 2) hippocampal sclerosis and from age-matched nonepileptic postmortem controls (n D 5). PTBR expression was assessed by immunohistochemistry and reverse-transcription polymerase chain reaction. Receptor sites were evaluated using an in vitro binding assay and the selective PTBR ligand [ 3 H]PK11195. Epileptic patients with hippocampal sclerosis showed increases in PTBR binding sites, im-munoreactivity, and mRNA expression compared to both nonsclerotic TLE patients and postmortem nonepileptic controls. Induction of PTBR expression and binding sites were directly correlated with the presence of hippocampal sclerosis and the accompanying reac-tive gliosis.

Identification of brain regions predicting epileptogenesis by serial [18F]GE-180 positron emission tomography imaging of neuroinflammation in a rat model of temporal lobe epilepsy

“…In this context, an immunohistochemistry analysis confirmed an overexpression of TSPO in surgical tissue (Sauvageau et al, 2002). Taking this into account efforts have also been made to assess epilepsy-associated alterations by clinical application of TSPO PET.…”

PET imaging of brain inflammation during early epileptogenesis in a rat model of temporal lobe epilepsy

“…Several studies utilising resected tissue from chronic epileptic patients have shown increased TSPO binding [5-7]. More recently, studies employing 11 C]-PK11195, although having inferior PET imaging characteristics (signal-to-noise ratio) than 18 F]-PBR111 [10], succeeded in identifying focal and diffuse regions of activated microglia in Rasmussen's encephalitis [30] and areas of focal cortical dysplasia [31].…”

“…Several groups have recently developed radioligands, which are translocator protein (TSPO) specific and potentially very interesting for clinical use. TSPO or previously named peripheral benzodiazepine receptor (PBR), which is a marker of activated glia, has been detected in surgically resected brain tissue and most recently in vivo with PET in patients with TLE [5-8]. Such biomarkers may become of particular value to aide in patient diagnoses and/or stratification, to evaluate the effect of new drug therapies on brain inflammation and for resective surgery of the epileptogenic zone [6,8].…”

Secreted phospholipase A2-IIA-induced a phenotype of activated microglia in BV-2 cells requires epidermal growth factor receptor transactivation and proHB-EGF shedding

“…Cerebral ischemia and other neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson’s disease, and multiple sclerosis, among others, are associated with proliferation and activation of microglia [2-6]. The activated microglia undergo dramatic morphological changes, from a resting ramified form to an activated amoeboid shape, and secrete a host of immunomodulatory and neurotoxic factors.…”