Molecular biology of the blood-brain and the blood-cerebrospinal fluid barriers: similarities and differences

Efficient processing of information by the central nervous system (CNS) represents an important evolutionary advantage. Thus, homeostatic mechanisms have developed that provide appropriate circumstances for neuronal signaling, including a highly controlled and stable microenvironment. To provide such a milieu for neurons, extracellular fluids of the CNS are separated from the changeable environment of blood at three major interfaces: at the brain capillaries by the blood-brain barrier (BBB), which is localized at the level of the endothelial cells and separates brain interstitial fluid (ISF) from blood; at the epithelial layer of four choroid plexuses, the blood-cerebrospinal fluid (CSF) barrier (BCSFB), which separates CSF from the CP ISF, and at the arachnoid barrier. The two barriers that represent the largest interface between blood and brain extracellular fluids, the BBB and the BCSFB, prevent the free paracellular diffusion of polar molecules by complex morphological features, including tight junctions (TJs) that interconnect the endothelial and epithelial cells, respectively. The first part of this review focuses on the molecular biology of TJs and adherens junctions in the brain capillary endothelial cells and in the CP epithelial cells. However, normal function of the CNS depends on a constant supply of essential molecules, like glucose and amino acids from the blood, exchange of electrolytes between brain extracellular fluids and blood, as well as on efficient removal of metabolic waste products and excess neurotransmitters from the brain ISF. Therefore, a number of specific transport proteins are expressed in brain capillary endothelial cells and CP epithelial cells that provide transport of nutrients and ions into the CNS and removal of waste products and ions from the CSF. The second part of this review concentrates on the molecular biology of various solute carrier (SLC) transport proteins at those two barriers and underlines differences in their expression between the two barriers. Also, many blood-borne molecules and xenobiotics can diffuse into brain ISF and then into neuronal membranes due to their physicochemical properties. Entry of these compounds could be detrimental for neural transmission and signalling. Thus, BBB and BCSFB express transport proteins that actively restrict entry of lipophilic and amphipathic substances from blood and/or remove those molecules from the brain extracellular fluids. The third part of this review concentrates on the molecular biology of ATP-binding cassette (ABC)-transporters and those SLC transporters that are involved in efflux transport of xenobiotics, their expression at the BBB and BCSFB and differences in expression in the two major blood-brain interfaces. In addition, transport and diffusion of ions by the BBB and CP epithelium are involved in the formation of fluid, the ISF and CSF, respectively, so the last part of this review discusses molecular biology of ion transporters/exchangers and ion channels in the brain endothelial and CP epithelial cells

The AdS 5 non-Abelian T-dual of Klebanov-Witten as a N=1 linear quiver from M5-branes

In this paper we study an $AdS_5$ solution constructed using non-Abelian T-duality, acting on the Klebanov-Witten background. We show that this is dual to a linear quiver with two tails of gauge groups of increasing rank. The field theory dynamics arises from a D4-NS5-NS5' brane set-up, generalizing the constructions discussed by Bah and Bobev. These realize $\mathcal{N}=1$ quiver gauge theories built out of $\mathcal{N}=1$ and $\mathcal{N}=2$ vector multiplets flowing to interacting fixed points in the infrared. We compute the central charge using $a$-maximization, and show its precise agreement with the holographic calculation. Our result exhibits $n^3$ scaling with the number of five-branes. This suggests an eleven-dimensional interpretation in terms of M5-branes, a generic feature of various $AdS$ backgrounds obtained via non-Abelian T-duality.Comment: 27 pages plus interesting appendixes and various figures. Improved quiver field theory proposa

Fullerol-Titania Charge-Transfer-Mediated Photocatalysis Working under Visible Light

The development of visible-light-active photocatalysts is being investigated through various approaches. In this study, C-60-based sensitized photocatalysis that works through the charge transfer (CT) mechanism is proposed and tested as a new approach. By employing the water-soluble fullerol (C-60(OH)(x)) instead Of C-60, we demonstrate that the adsorbed fullerol activates TiO2 under visible-light irradiation through the "surface-complex CT" mechanism, which is largely absent in the C-60/TiO2 system. Although fullerene and. its derivatives have often been utilized in TiO2-based photochemical conversion systems as an electron transfer relay, their successful photocatalytic application as a visible-light sensitizer of TiO2 is not well established. Fullerol/TiO2 exhibits marked visible photocatalytic activity not only for the redox conversion of 4-chlorophenol, I-, and Cr-VI, but also for H-2 production. The photoclectrode of fullerol/TiO2 also generates an enhanced anodic photocurrent under visible light as compared with the electrodes of bare TiO2 and C60/TiO2, which confirms that the visible-light-induced electron transfer from fullerol to TiO2 is particularly enhanced. The surface complexation of fullerol/TiO2 induced a visible absorption band around 400-500 nm, which was extinguished when the adsorption of fullerol was inhibited by fluorination of the surface of TiO2. The transient absorption spectroscopic measurement gave an absorption spectrum ascribed to fullerol radical cations (fullerol(center dot+)) the generation of which should be accompanied by the proposed CT. The theoretical calculation regarding the absorption spectra for the (TiO2 cluster + fullerol) model also confirmed the proposed CT, which involves excitation from HOMO (fullerol) to LUMO (TiO2 cluster) as the origin of the visible-light absorption.X117370sciescopu