The Role of Peripheral Benzodiazepine Receptors (PBRs) in CNS Pathophysiology

Abstract

The peripheral benzodiazepine receptors (PBRs) have been identified to bind selectively benzodiazepine ligands and an isoquinoline carboxamide derivative PK 11195 with high affinity. PBRs are present in the central nervous system (CNS), peripheral tissues, and most organs in the human body. PBRs are different from the central benzodiazepine receptors (CBRs) related to the nerve cell membrane GABA(A) receptor and are thought to play several physiological and pathophysiological functions in the CNS and immune system due to their meanly localization in glial cells, the mitochondrial outer membrane of peripheral cells and blood leucocytes and to their important roles in steroidogenesis, cell proliferation and differentiation. Recent research has shown that the density of PBRs is significantly increased in CNS several disorders, such as epilepsy, multiple sclerosis, cerebral ischemia, astrocytoma, brain injury and neurodegenerative diseases. Recent progress in the pharmacology of PBRs is reviewed here with respect to the functions in the brain and peripheral tissues including apoptosis, immune system modulation, seizure promotion, reactions of anticonvulsants on peripheral blood cells, and adverse drug reactions (ADR) of anticonvulsants.

MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity

“…In the CNS, PBRs are mainly located in glial cells, particularly in microglia and astrocytes, with highest densities in the olfactory bulb, choroid plexus, and the ependymal lining of the ventricles [17,30]. In the CNS, PBRs participate in multiple physiological functions including neurosteroid synthesis, nutritional support of neurons, and modulation of CNS immune reactions.…”

“…Activation of microglia also may indicate that they are performing some protective functions such as releasing neurotrophic factors and protecting cells from damage [32,34,35]. Various studies have demonstrated that PBRs are involved in numerous nervous system disorders such as multiple sclerosis, cerebral ischemia and stroke, epilepsy, brain injury, neurotoxic brain damage, and neurodegenerative diseases [17,[34][35][36][37].…”

“…After brain injury, immunolabelling of PBRs has been shown to increase with the increase being localized to mitochondria and other cellular compartments [17,38,39].…”

“…In order to obtain sufficient data from living animals and longitudinally assess the neurotoxic effects associated with developmental exposures to anesthesia, we have developed a microPET protocol thought to target neuronal damage in vivo using imaging approaches [15,16]. Since levels of the peripheral benzodiazepine receptor (PBR) are thought to increase in areas of neuronal injury following exposure to neurotoxicants [17], the PBR is widely recognized as an important target for imaging via PET [17][18][19]. In this study, …”

Assessment of Potential Neuronal Toxicity of Inhaled Anesthetics in the Developing Nonhuman Primate

“…In the CNS, PBRs are mainly located in glial cells, particularly in microglia and astrocytes, with the highest densities in the olfactory bulb, choroid plexus, and ependymal lining of the ventricles [14,11]. In the CNS, PBRs participate in multiple physiological functions including neurosteroid synthesis, nutritional support of neurons and modulation of CNS immune reactions.…”