The peripheral-type benzodiazepine receptor and the cardiovascular system. Implications for drug development

Imaging Brain Inflammation with [11C]PK11195 by PET and Induction of the Peripheral-Type Benzodiazepine Receptor after Transient Focal Ischemia in Rats

“…In contrast, in other studies, PBR upregulation has been associated with cell survival (Rey et al, 2000). In addition to its possible role in mitochondrial function and mitochondrial-driven apoptosis, PBR participates in a wide variety of functions such as synthesis of steroids, transport of cholesterol, porphyrin transport and heme synthesis, and immunomodulation (see reviews by Papadopoulos et al, 2006;Veenman and Gavish, 2006). The multiple functions of PBR, the lack of knowledge about its exact role in reactive glia and macrophages, and the present finding showing heterogeneous levels of cellular expression after cerebral ischemia indicate that PBR remains an intricate target for imaging brain inflammation.…”

The lack of expression of the peripheral benzodiazepine receptor characterises microglial response in anaplastic astrocytomas

“…Positive immunohistochemical reactions obtained with adrenal gland, MS and PD confirmed that the anti-PBR antibody 8D7 is suitable for routinely processed tissue and the search in protein Blast/Fasta, and Western-blot analysis confirmed its specificity. Finally, PBR immunolabelling in tumour cells and intravascular and leptomeningeal mononuclear inflammatory cells that normally produce PBR [13,23] indicated good preservation of the antigen in tumour samples. Taken altogether, these findings confirmed that the very low-PET signal and the lack of immunolabelling in tumour tissue were consistent with a very low expression of PBR in tumour tissue.…”

“…These samples were previously immunostained for MHCII antigen and they were known to contain activated microglial cells. Lymphocytes, neutrophils, endothelial cells and smooth muscle cells present within tumour tissues were considered internal positive controls, as they are known to constitutively express PBR [13,23].…”

“…For this reason, high levels of PBR are generally considered a marker of microglial activation [5], and the PBRspecific ligand [ 11 C](R)-PK11195 is widely used in positron emission tomography (PET) studies to trace microglial infiltrate as an in vivo indicator of tissue damage [11]. Also known as PK-11195 binding protein or translocator protein, the PBR is an 18 kDa molecule consisting of a five helices spanning the membrane lipid bilayer of the outer mitochondrial membrane and forming a heterotrimer together with a voltage dependent anion channel and an adenine nucleotide transporter [12,13]. The PBR is expressed in several normal tissues with the highest levels in gonads and cortical cells of adrenal gland [14,15] and its major function is to actively transport cholesterol and proteins through the mitochondrial membrane [13].…”

“…Also known as PK-11195 binding protein or translocator protein, the PBR is an 18 kDa molecule consisting of a five helices spanning the membrane lipid bilayer of the outer mitochondrial membrane and forming a heterotrimer together with a voltage dependent anion channel and an adenine nucleotide transporter [12,13]. The PBR is expressed in several normal tissues with the highest levels in gonads and cortical cells of adrenal gland [14,15] and its major function is to actively transport cholesterol and proteins through the mitochondrial membrane [13]. The actual role of PBR in microglial cells is still to be elucidated although recent studies in vitro [16] and animal model [17] suggested that it may exert a pro-inflammatory function.…”