Search results for "BLOOD-BRAIN BARRIER"
showing 10 items of 141 documents
Refining in vitro neurotoxicity testing--the development of blood-brain barrier models.
2003
The purpose of this paper is to review the current state of development of advanced in vitro blood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivo functions of the BBB in an effective way. With a BBB…
Neuronal and BBB damage induced by sera from patients with secondary progressive multiple sclerosis.
2009
An important component of the pathogenic process of multiple sclerosis (MS) is the blood-brain barrier (BBB) damage. We recently set an in vitro model of BBB, based on a three-cell-type co-culture system, in which rat neurons and astrocytes synergistically induce brain capillary endothelial cells to form a monolayer with permeability properties resembling those of the physiological BBB. Herein we report that the serum from patients with secondary progressive multiple sclerosis (SPMS) has a damaging effect on isolated neurons. This finding suggests that neuronal damaging in MS could be a primary event and not only secondary to myelin damage, as generally assumed. SPMS serum affects the perme…
Extracellular space and electrolyte distribution in cortex and white matter of dog brain in cold induced oedema
1973
24 hours after a circumscribed cold injury of the cortex dog brains were perfused from the lateral ventricle and the frontal subarachnoidal space to the cisterna magna with an artificial CSF containing trace amounts of35S-labelled thiosulphate. Simultaneously the extracellular tracer was administered intravenously. Extracellular fluid volume was estimated and found to be increased from 10 to 15% in the oedematous cortex and from 10 to 27% in the oedematous white matter. The actual size of ECS in oedematous white matter, however, must be larger as indicated by the relative alterations of thiosulphate distribution, tissue water, sodium and chloride. Apparently a small part of the fluid accumu…
The Blood–Brain Barrier as a Target in Traumatic Brain Injury Treatment
2014
Traumatic brain injury (TBI) is one of the most frequent causes of death in the young population. Several clinical trials have unsuccessfully focused on direct neuroprotective therapies. Recently immunotherapeutic strategies shifted into focus of translational research in acute CNS diseases. Cross-talk between activated microglia and blood–brain barrier (BBB) could initiate opening of the BBB and subsequent recruitment of systemic immune cells and mediators into the brain. Stabilization of the BBB after TBI could be a promising strategy to limit neuronal inflammation, secondary brain damage and acute neurodegeneration. This review provides an overview on the pathophysiology of TBI and brain…
Multiparametric magnetic resonance in the assessment of the gender differences in a high-grade glioma rat model
2014
This is an Open Access article distributed under the terms of the Creative Commons Attribution License.
Fingolimod (FTY720-P) Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro Model
2015
Breakdown of the blood-brain barrier (BBB) is an early hallmark of multiple sclerosis (MS), a progressive inflammatory disease of the central nervous system. Cell adhesion in the BBB is modulated by sphingosine-1-phosphate (S1P), a signaling protein, via S1P receptors (S1P\(_1\)). Fingolimod phosphate (FTY720-P) a functional S1P\(_1\) antagonist has been shown to improve the relapse rate in relapsing-remitting MS by preventing the egress of lymphocytes from lymph nodes. However, its role in modulating BBB permeabilityin particular, on the tight junction proteins occludin, claudin 5 and ZO-1has not been well elucidated to date. In the present study, FTY720-P did not change the transendotheli…
The close link between brain vascular pathological conditions and neurodegenerative diseases: Focus on some examples and potential treatments
2022
A close relationship is emerging among the age-related neurodegenerative decline, and the age-related typical alterations, dysfunctions, and related diseases of the cerobro-and/or cardiovascular system, which contributes in a significative manner to the triggering and progressing of neurodegenerative diseases (NeuroDegD). Specifically, macroinfarcts, microinfarcts, micro-hemorrhages (and particularly their number), atherosclerosis, arteriolosclerosis and cerebral amyloid angiopathy have been documented to be significantly associated with the onset of the cognitive impairment. In addition, vascular alterations and dysfunctions resulting in a reduced cerebral blood flow, and anomalies in the …
Image-Guided Synthesis Reveals Potent Blood-Brain Barrier Permeable Histone Deacetylase Inhibitors
2014
Recent studies have revealed that several histone deacetylase (HDAC) inhibitors, which are used to study/treat brain diseases, show low blood-brain barrier (BBB) penetration. In addition to low HDAC potency and selectivity observed, poor brain penetrance may account for the high doses needed to achieve therapeutic efficacy. Here we report the development and evaluation of highly potent and blood-brain barrier permeable HDAC inhibitors for CNS applications based on an image-guided approach involving the parallel synthesis and radiolabeling of a series of compounds based on the benzamide HDAC inhibitor, MS-275 as a template. BBB penetration was optimized by rapid carbon-11 labeling and PET im…
Na+ -dependent neutral amino acid transporters A, ASC, and N of the blood-brain barrier: mechanisms for neutral amino acid removal.
2004
Four Na+-dependent transporters of neutral amino acids (NAA) are known to exist in the abluminal membranes (brain side) of the blood-brain barrier (BBB). This article describes the kinetic characteristics of systems A, ASC, and N that, together with the recently described Na+-dependent system for large NAA (Na+-LNAA), provide a basis for understanding the functional organization of the BBB. The data demonstrate that system A is voltage dependent (3 positive charges accompany each molecule of substrate). Systems ASC and N are not voltage dependent. Each NAA is a putative substrate for at least one system, and several NAA are transported by as many as three. System A transports Pro, Ala, His,…
Uptake of polymeric nanoparticles in a human induced pluripotent stem cell-based blood-brain barrier model: Impact of size, material, and protein cor…
2021
The blood–brain barrier (BBB) maintains the homeostasis of the central nervous system, which is one of the reasons for the treatments of brain disorders being challenging in nature. Nanoparticles (NPs) have been seen as potential drug delivery systems to the brain overcoming the tight barrier of endothelial cells. Using a BBB model system based on human induced pluripotent stem cells (iPSCs), the impact of polymeric nanoparticles has been studied in relation to nanoparticle size, material, and protein corona. PLGA [poly(lactic-co-glycolic acid)] and PLLA [poly(d,l-lactide)] nanoparticles stabilized with Tween® 80 were synthesized (50 and 100 nm). iPSCs were differentiated into human brain m…