Confounding Parameters in Preclinical Assessment of Blood–Brain Barrier Permeation: An Overview With Emphasis on Species Differences and Effect of Disease States

2013 ◽  
Vol 10 (5) ◽  
pp. 1581-1595 ◽  
Author(s):  
Anand K. Deo ◽  
Frank-Peter Theil ◽  
Jean-Marie Nicolas
Author(s):  
Aaron Dadas ◽  
Jolewis Washington ◽  
Nicola Marchi ◽  
Damir Janigro

2010 ◽  
Vol 30 (9) ◽  
pp. 1625-1636 ◽  
Author(s):  
Jeffrey J Lochhead ◽  
Gwen McCaffrey ◽  
Colleen E Quigley ◽  
Jessica Finch ◽  
Kristin M DeMarco ◽  
...  

The blood–brain barrier (BBB) has a critical role in central nervous system homeostasis. Intercellular tight junction (TJ) protein complexes of the brain microvasculature limit paracellular diffusion of substances from the blood into the brain. Hypoxia and reoxygenation (HR) is a central component to numerous disease states and pathologic conditions. We have previously shown that HR can influence the permeability of the BBB as well as the critical TJ protein occludin. During HR, free radicals are produced, which may lead to oxidative stress. Using the free radical scavenger tempol (200 mg/kg, intraperitoneal), we show that oxidative stress produced during HR (6% O2 for 1 h, followed by room air for 20 min) mediates an increase in BBB permeability in vivo using in situ brain perfusion. We also show that these changes are associated with alterations in the structure and localization of occludin. Our data indicate that oxidative stress is associated with movement of occludin away from the TJ. Furthermore, subcellular fractionation of cerebral microvessels reveals alterations in occludin oligomeric assemblies in TJ associated with plasma membrane lipid rafts. Our data suggest that pharmacological inhibition of disease states with an HR component may help preserve BBB functional integrity.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Richard F. Keep ◽  
Hazel C. Jones ◽  
Lester R. Drewes

AbstractThis editorial discusses advances in brain barrier and brain fluid research in 2020. Topics include: the cerebral endothelium and the neurovascular unit; the choroid plexus; the meninges; cerebrospinal fluid and the glymphatic system; disease states impacting the brain barriers and brain fluids; drug delivery to the brain. This editorial also highlights the recently completed Fluids Barriers CNS thematic series entitled, ‘Advances in in vitro modeling of the blood–brain barrier and neurovascular unit’. Such in vitro modeling is progressing rapidly.


PEDIATRICS ◽  
1967 ◽  
Vol 39 (3) ◽  
pp. 463-464
Author(s):  
IVAN DIAMOND

It is, of course, well-known that the newborn guinea pig has a relatively mature central nervous system but this may have little to do with the functional characteristics of the blood-brain barrier for bilirubin and other organic compounds. For example, although the maturing brain of guinea pigs, mice, rats, cats, and humans shows marked metabolic differences, in these mammals a number of substances are regularly excluded from the brain at all stages of development. Thus, despite species differences and "the changing metabolic pattern of a given specie" the blood-brain barrier for certain compounds is functionally intact in the fetus, newborn, and adult.


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