AnalyzeDirect

The blood-brain barrier is an anatomical interface developed to separate and protect the brain from the circulatory system. The brain’s network of blood vessels allows the transport of neurotransmitters, glucose, essential nutrients and hormones across the brain, while it blocks other substances from penetrating. This barrier is so efficient at protecting the brain against the passage of unfamiliar substances that it often prevents life-saving drugs from being able to reach the brain.

Aiming to find new ways for medicines to bypass this barrier and enter the brain, scientists from the Medical University of Vienna, Austria, focused their research on the inhibition of P-glycoprotein, a transport protein. This transmembrane pump plays a crucial role in limiting cellular uptake of drugs from blood circulation into the brain as it sends these compounds back into the capillaries. Recruiting five healthy males, the researchers investigated how the infusion of an experimental P-glycoprotein inhibitor (tariquidar) affected the brain distribution of verapamil, a substance that is pumped back into the vessels by P-glycoprotein.

The evaluation of PET and MRI images, which were coregistered and processed using Analyze software, indicated that the suppression of P-glycoprotein function resulted in a substantial increase in the amount of P-glycoprotein substrate in the brain. Comparing the distribution of the compound in the brain with its uptake in the pituitary gland, a structure that is not protected by the blood-brain barrier, the researchers were able to predict the maximum uptake possible due to complete inhibition of P-glycoprotein. The similarity of these two values showed that the inhibitor was able to induce good to excellent supression of P-glycoprotein activity.

Findings from this study may lead to better treatments for some of the most challenging brain diseases, improving brain penetration of therapeutic drugs through P-glycoprotein inhibition at the blood-brain barrier.

Tags: Brain Studies