Measuring Blood-brain-barrier Permeability Using Evans Blue in Mice

BIO-PROTOCOL ◽  
2015 ◽  
Vol 5 (15) ◽  
Author(s):  
Jun-Xia Yang ◽  
Yan-Yu Jiang ◽  
Yu-Bai Guo
Author(s):  
Daniel J. Cole ◽  
John C. Drummond ◽  
Jerry S. Matsumura ◽  
Suzzanne Marcantonio ◽  
Bonnie I. Chi-Lum

ABSTRACT:The effect of hypervolemic-hemodilution, with and without hypertension, on blood-brain barrier permeability was investigated in rats, after 180 minutes of middle cerebral artery occlusion (MCAo), and 60 minutes of reperfusion. One of the following conditions was maintained during MCAo: 1) Control — hematocrit and blood pressure were not manipulated; 2) Hypervolemic-Hemodilution/Normotension — the hematocrit was decreased to 30%; 3) Hypervolemic-Hemodilution/Hypertension — the hematocrit was decreased to 30% and mean arterial pressure increased by 30 mmHg with phenylphrine. In all groups, Evans Blue was administered, and its concentration determined by spectrophotometric assay. Evans Blue (μg{g-1 of brain tissue [mean ± SD]) was greater in the Hypervolemic- Hemodilution/Hypertension group (71 ± 20) versus the Control (13 ± 9) and Hypervolemic-Hemodilution/ Normotension (17 ± 10) groups (p < 0.05). No other differences were present. These results support the hypothesis that during MCAo, hypervolemic-hemodilution/hypertensive therapy effects an increase in blood-brain barrier permeability in the early period of reperfusion.


2001 ◽  
Vol 79 (9) ◽  
pp. 793-798 ◽  
Author(s):  
Mehmet Kaya ◽  
Mutlu Küçük ◽  
Rivaze Bulut Kalayci ◽  
Vedat Cimen ◽  
Candan Gürses ◽  
...  

Magnesium probably protects brain tissue against the effects of cerebral ischemia, brain injury and stroke through its actions as a calcium antagonist and inhibitor of excitatory amino acids. The effects of magnesium sulfate on cerebrovascular permeability to a dye, Evans blue, were studied during insulin-induced hypoglycemia with hypothermia in rats. Hypoglycemia was induced by an intramuscular injection of insulin. After giving insulin, each animal received MgSO4 (270 mg/kg) ip, followed by a 27 mg/kg dose every 20 min for 2.5 h. Plasma glucose and Mg2+ levels of animals were measured. Magnesium concentrations increased in the serum following MgSO4 administration (6.05 ± 0.57 vs. 2.58 ± 0.14 mg/dL in the Mg2+ group, and 7.14 ± 0.42 vs. 2.78 ± 0.06 mg/dL in the insulin + Mg2+ group, P < 0.01). Plasma glucose levels decreased following hypoglycemia (4 ± 0.66 vs. 118 ± 2.23 mg/dL in the insulin group, and 7 ± 1.59 vs. 118 ± 4.84 mg/dL in the insulin + Mg2+ group, P < 0.01). Blood-brain barrier permeability to Evans blue considerably increased in hypoglycemic rats (P < 0.01). In contrast, blood-brain barrier permeability to Evans blue was significantly reduced in treatment of hypoglycemic rats with MgSO4 (P < 0.01). These results indicate that Mg2+ greatly reduced the passage of exogenous vascular tracer bound to albumin into the brain during hypoglycemia with hypothermia. Mg2+ could have protective effects on blood-brain barrier permeability against insulin-induced hypoglycemia.Key words: blood-brain barrier, hypoglycemia, Mg2+, Evans-blue.


2018 ◽  
Vol 25 (9) ◽  
pp. 1073-1089 ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte

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.


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