Search results for "BLOOD-BRAIN BARRIER"

LRP1 mediates bidirectional transcytosis of amyloid-β across the blood-brain barrier.

2011

According to the "amyloid hypothesis", the amyloid-β (Aβ) peptide is the toxic intermediate driving Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that the low density lipoprotein receptor-related protein 1 (LRP1) transcytoses Aβ out of the brain across the blood-brain barrier (BBB). To provide genetic evidence for LRP1-mediated transcytosis of Aβ across the BBB we analyzed Aβ transcytosis across primary mouse brain capillary endothelial cells (pMBCECs) derived from wild-type and LRP1 knock-in mice. Here, we show that pMBCECs in vitro express functionally active LRP1. Moreover, we demonstrate that LRP1 mediates transcytosis of [(125)I]-Aβ(1-40) across pMBCECs in both direct…

Cationic amino acid transport across the blood-brain barrier is mediated exclusively by system y+.

2006

Cationic amino acid (CAA) transport is brought about by two families of proteins that are found in various tissues: Cat (CAA transporter), referred to as system y+, and Bat [broad-scope amino acid (AA) transporter], which comprises systems b0,+, B0,+, and y+L. CAA traverse the blood-brain barrier (BBB), but experiments done in vivo have only been able to examine the BBB from the luminal (blood-facing) side. In the present study, plasma membranes isolated from bovine brain microvessels were used to identify and characterize the CAA transporter(s) on both sides of the BBB. From these studies, it was concluded that system y+was the only transporter present, with a prevalence of activity on the…

Cellular Prion Protein Participates in Amyloid-β Transcytosis across the Blood—Brain Barrier

2012

The blood—brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1–40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1–40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.

Uptake mechanism of ApoE-modified nanoparticles on brain capillary endothelial cells as a blood-brain barrier model.

2012

Background The blood-brain barrier (BBB) represents an insurmountable obstacle for most drugs thus obstructing an effective treatment of many brain diseases. One solution for overcoming this barrier is a transport by binding of these drugs to surface-modified nanoparticles. Especially apolipoprotein E (ApoE) appears to play a major role in the nanoparticle-mediated drug transport across the BBB. However, at present the underlying mechanism is incompletely understood. Methodology/Principal Findings In this study, the uptake of the ApoE-modified nanoparticles into the brain capillary endothelial cells was investigated to differentiate between active and passive uptake mechanism by flow cytome…

EFFECT OF SERA FROM PATIENTS WITH MULTIPLE SCLEROSIS ON A BLOOD-BRAIN BARRIER IN VITRO MODEL.

2009

Pyroglutamate stimulates Na+ -dependent glutamate transport across the blood-brain barrier.

2006

Regulation of Na(+)-dependent glutamate transport was studied in isolated luminal and abluminal plasma membranes derived from the bovine blood-brain barrier. Abluminal membranes have Na(+)-dependent glutamate transporters while luminal membranes have facilitative transporters. This organization allows glutamate to be actively removed from brain. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle (GGC), is on the luminal membrane. Pyroglutamate (oxoproline), an intracellular product of GGC, stimulated Na(+)-dependent transport of glutamate by 46%, whereas facilitative glutamate uptake in luminal membranes was inhibited. This relationship between GGC and glutamate tra…

Meprin β: A novel regulator of blood–brain barrier integrity

2020

The metalloprotease meprin β (Mep1b) is capable of cleaving cell-adhesion molecules in different tissues (e.g. skin, kidney and intestine) and is dysregulated in several diseases associated with barrier breakdown (Alzheimer´s disease, kidney disruption, inflammatory bowel disease). In this study, we demonstrate that Mep1b is a novel regulator of tight junction (TJ) composition and blood–brain barrier (BBB) integrity in brain endothelium. In Mep1b-transfected mouse brain endothelial cells (bEnd.3), we observed a reduction of the TJ protein claudin-5, decreased transendothelial electrical resistance (TEER) and an elevated permeability to paracellular diffusion marker [14C]-inulin. Analysis o…

Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice

2010

Abstract Background P-glycoprotein (P-gp), an efflux transporter localized in the blood–brain barrier, limits the access of multiple xenobiotics to the central nervous system (CNS). For the new antipsychotic aripiprazole and its active metabolite dehydroaripiprazole differences in disposition in blood and brain were investigated after acute and sub-chronic administration in a P-gp knockout mouse model. Methods Serum and brain concentrations of both drugs were measured at several time points 1–24 h after i.p. injection of 10 mg/kg aripiprazole and after 11 days of sub-chronic administration in several tissues. Moreover, the expression of P-gp was determined by Western blot analysis after sub…

Experimental investigations on a model of cryogenic edema.

1987

The role of mechanisms underlying formation and progression of vasogenic brain edema is investigated. On this purpose, cerebral edema was produced by cortical freezing in two different brain situations in rabbits (with or without replacement of bone flap). BBB (Blood-Brain Barrier) breakdown was evaluated by observation of Evans blue extravation, while a histopathological evaluation was carried out by light and transmission electron microscopy. Water content of brain tissue was determined by the wet/dry weight ratio method. Comparison of extension and intensity of cerebral edema between these two groups of animals shows a statistically significant difference: there was evidence of higher wa…

A Neuroprotective Function for the Hematopoietic Protein Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

2007

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic cytokine responsible for the proliferation, differentiation, and maturation of cells of the myeloid lineage, which was cloned more than 20 years ago. Here we uncovered a novel function of GM-CSF in the central nervous system (CNS). We identified the GM-CSF α-receptor as an upregulated gene in a screen for ischemia-induced genes in the cortex. This receptor is broadly expressed on neurons throughout the brain together with its ligand and induced by ischemic insults. In primary cortical neurons and human neuroblastoma cells, GM-CSF counteracts programmed cell death and induces BCL-2 and BCL-Xl expression in a dose- a…