Lipids in Blood-Brain Barrier Models in vitro II: Influence of Glial Cells on Lipid Classes and Lipid Fatty Acids

At high concentrations, glutamate (Glu) exerts potent neurotoxic properties, leading to irreversible brain damages found in numerous neurological disorders. The accepted notion that Glu homeostasis in brain interstitial fluid is maintained primarily through the activity of Glu transporters present on glial cells does not take into account the possible contribution of endothelial cells constituting the blood-brain barrier (BBB) to this process. Here, we present evidence for the presence of the Glu transporters, excitatory amino-acid transporters (EAATs) 1 to 3, in porcine brain endothelial cells (PBECs) and show their participation in Glu uptake into PBECs. Moreover, transport of Glu across three in vitro models of the BBB is investigated for the first time, and evidence for Glu transport across the BBB in both directions is presented. Our results provide evidence that the BBB can function in the efflux mode to selectively remove Glu, via specific transporters, from the abluminal side (brain) into the luminal compartment (blood). Furthermore, we found that glial cells lining the BBB have an active role in the efflux process by taking up Glu and releasing it, through hemichannels, anion channels, and possibly the reversal of its EAATs, in close proximity to ECs, which in turn take up Glu and release it to the blood.

Download Full-text

Contribution of glial cells and pericytes to the mRNA profiles of P-glycoprotein and multidrug resistance-associated proteins in an in vitro model of the blood–brain barrier

Brain Research ◽

10.1016/j.brainres.2004.05.092 ◽

2004 ◽

Vol 1018 (1) ◽

pp. 1-9 ◽

Cited By ~ 100

Author(s):

Vincent Berezowski ◽

Christophe Landry ◽

Marie-Pierre Dehouck ◽

Roméo Cecchelli ◽

Laurence Fenart

Keyword(s):

Multidrug Resistance ◽

Blood Brain Barrier ◽

Glial Cells ◽

In Vitro Model ◽

Brain Barrier ◽

P Glycoprotein ◽

Blood Brain ◽

Associated Proteins ◽

Vitro Model

Download Full-text

Stroke-Induced Brain Parenchymal Injury Drives Blood–Brain Barrier Early Leakage Kinetics: A Combined in Vivo/in Vitro Study

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2013.169 ◽

2013 ◽

Vol 34 (1) ◽

pp. 95-107 ◽

Cited By ~ 41

Author(s):

Mélanie Kuntz ◽

Caroline Mysiorek ◽

Olivier Pétrault ◽

Maud Pétrault ◽

Rustem Uzbekov ◽

...

Keyword(s):

Blood Brain Barrier ◽

Glial Cells ◽

Glucose Deprivation ◽

Brain Barrier ◽

Imaging Method ◽

Early Reperfusion ◽

Blood Brain ◽

Brain Parenchymal

The disappointing clinical outcomes of neuroprotectants challenge the relevance of preclinical stroke models and data in defining early cerebrovascular events as potential therapeutic targets. The kinetics of blood–brain barrier (BBB) leakage after reperfusion and the link with parenchymal lesion remain debated. By using in vivo and in vitro approaches, we conducted a kinetic analysis of BBB dysfunction during early reperfusion. After 60 minutes of middle cerebral artery occlusion followed by reperfusion times up to 24 hours in mice, a non-invasive magnetic resonance imaging method, through an original sequence of diffusion-weighted imaging, determined brain water mobility in microvascular compartments ( D∗) apart from parenchymal compartments (apparent diffusion coefficient). An increase in D∗ found at 4 hours post reperfusion concurred with the onset of both Evans blue/Dextran extravasations and in vitro BBB opening under oxygen-glucose deprivation and reoxygenation ( R). The BBB leakage coincided with an emerging cell death in brain tissue as well as in activated glial cells in vitro. The co-culture of BBB endothelial and glial cells evidenced a recovery of endothelium tightness when glial cells were absent or non-injured during R. Preserving the ischemic brain parenchymal cells within 4 hours of reperfusion may improve therapeutic strategies for cerebrovascular protection against stroke.

Download Full-text