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"Flat Tire" Technique Identifies Leaks in the Blood–Brain Barrier

The blood-brain barrier with blood vessels shown in pink and nuclei in blue.
The blood-brain barrier. Credit: Emily Wyatt, Mark Davis/ California Institute of Technology
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In epilepsy research, it has long been assumed that a leaky blood-brain barrier is a cause of inflammation in the brain. Using a novel method, researchers from Bonn University Hospital (UKB) and the University of Bonn have demonstrated that the barrier between the blood and the central nervous system remains largely intact. The approach of their study provides important insights into the development of epilepsy and could significantly optimize drug development in the pharmaceutical industry. The study results have recently been published in the renowned journal "Nature Communications".

500 kilometers of vessels in the human brain are lined with ten square meters of thin cell layer - the blood-brain barrier (BBB). This barrier protects the brain against harmful substances as well as pathogens. It also links the brain to the other organs in the body. If this selective barrier is leaky, diseases such as Parkinson's, multiple sclerosis, Alzheimer's could develop. Malfunctions of the BBB also play an important role in brain tumors. Researchers at the UKB and the University of Bonn want to get to the bottom of these interactions. To study BBB transport at the cellular level, they developed micropipette-based local perfusion of capillaries, i.e. finest blood vessels, in acute brain slices and combined it with multiphoton microscopy.

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Prof. Dirk Dietrich, head of the experimental neurosurgery section at the Clinic of Neurosurgery at the UKB, compares the new analysis technique of the blood-brain barrier investigated in the study to a flat bicycle tire: "If the tire loses air, you don't know where the leak is. That's why you hold the inflated bicycle tube under water to identify the leak. This principle also underlies our method." The researchers use a micropipette to fill the microscopic blood vessels with a liquid from the inside. Leaks are then visible to them under the multiphoton microscope.

His colleague Alf Lamprecht, Professor of Pharmaceutical Technology and Biopharmacy at the Pharmaceutical Institute of the University of Bonn, hopes that the new method could advance early drug development: "When a new active ingredient is developed, the question always arises as to whether and, above all, how it passes the blood-brain barrier. Identifying these transport mechanisms and barriers is enormously important for making the drug available in the brain." The results of the current study have potential to solve this problem in pharmacy. First author of the published article Dr. Amira Hanafy, a postdoctoral fellow at UKB's Clinic of Neurosurgery, sums up: "With the method we developed, we have a good tool to evaluate whether active ingredients reach the brain."

Reference: Hanafy AS, Steinlein P, Pitsch J, et al. Subcellular analysis of blood-brain barrier function by micro-impalement of vessels in acute brain slices. Nat Commun. 2023;14(1):481. doi: 10.1038/s41467-023-36070-6

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