scholarly journals Evaluating Permeability Surface-Area Product as a Measure of Blood-Brain Barrier Permeability in a Murine Model

2016 ◽  
Vol 37 (7) ◽  
pp. 1267-1274 ◽  
Author(s):  
E. K. Weidman ◽  
C. P. Foley ◽  
O. Kallas ◽  
J. P. Dyke ◽  
A. Gupta ◽  
...  
Keyword(s):  
Surface Area ◽  
Blood Brain Barrier ◽  
Murine Model ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Permeability Surface ◽  
Brain Barrier Permeability ◽  
Area Product

Blood-brain barrier permeability to sucrose and dextran after osmotic opening

1984 ◽  
Vol 247 (4) ◽  
pp. R634-R638 ◽  
Author(s):  
Y. Z. Ziylan ◽  
P. J. Robinson ◽  
S. I. Rapoport
Keyword(s):  
Blood Brain Barrier ◽  
Brain Regions ◽  
Brain Barrier ◽  
Differential Rate ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Size Dependent ◽  
Blood Brain ◽  
Permeability Surface ◽  
Brain Barrier Permeability

Regional cerebrovascular permeability-surface area (PA) products were calculated for two nonelectrolyte tracers differing considerably in molecular weight and size [( 14C]sucrose: mol wt 340 daltons, radius 5 A; and [3H]dextran: mol wt approximately 79,000 daltons, radius approximately 65 A) in control (uninfused) rats and in rats 6, 35, and 55 min after the blood-brain barrier was opened by a 30-s infusion of 1.8 molal L(+)-arabinose into a carotid artery. In control brain regions, mean PA for [14C]sucrose was 10(-5) s-1, whereas PA was not measurable for [3H]dextran. Six minutes after arabinose infusion, PA for both substances increased dramatically to 10(-4) s-1 or more; PA then declined at 35 and 55 min after arabinose infusion, but more markedly for [3H]dextran than for [14C]sucrose. The results demonstrate a size-dependent, differential rate of closure of the blood-brain barrier after osmotic opening. This is shown to be consistent with a pore model with bulk flow for blood-brain barrier permeability after osmotic opening.

Ligand and Structure-based Modeling of Passive Diffusion through the Blood-Brain Barrier

2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Blood Brain Barrier ◽  
In Silico ◽  
Passive Diffusion ◽  
Brain Barrier ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability ◽  
Different Types ◽  
The Brain

Background: Blood-brain barrier transport is an important process to be considered in drug candidates. The blood-brain barrier protects the brain from toxicological agents and, therefore, also establishes a restrictive mechanism for the delivery of drugs into the brain. Although there are different and complex mechanisms implicated in drug transport, in this review we focused on the prediction of passive diffusion through the blood-brain barrier. Methods: We elaborated on ligand-based and structure-based models that have been described to predict the blood-brain barrier permeability. Results: Multiple 2D and 3D QSPR/QSAR models and integrative approaches have been published to establish quantitative and qualitative relationships with the blood-brain barrier permeability. We explained different types of descriptors that correlate with passive diffusion along with data analysis methods. Moreover, we discussed the applicability of other types of molecular structure-based simulations, such as molecular dynamics, and their implications in the prediction of passive diffusion. Challenges and limitations of experimental measurements of permeability and in silico predictive methods were also described. Conclusion: Improvements in the prediction of blood-brain barrier permeability from different types of in silico models are crucial to optimize the process of Central Nervous System drug discovery and development.

Sign in / Sign up

Export Citation Format

Share Document