They subjected the barrier to oxygen-glucose deprivation, as happens when someone is having a stroke. In a study, published recently in the journal Advanced Science, the researchers presented and tested their new in vitro blood-brain barrier model. Hierlemann explains the benefit of this setup: “Since we are not using any pumps, we can experiment with multiple model systems simultaneously, for instance in an incubator, without increasing the setup complexity.” Gravity then triggered the flow, which-in turn-generated shear force on the cells. To mimic the way fluid flows in the body, the researchers realized the microfluidic platform with fluid reservoirs at both ends on a kind of seesaw. Transparent electrodes offer a decisive advantage over other types of electrodes, which include metal films or wire structures that may interfere with optical detection and high-resolution microscopy.
To facilitate this double act, the researchers deposited entirely transparent electrodes on glass coverslips on both sides of the barrier to measure its permeability, which is reflected in the electrical resistance across the cell barrier. “But what’s really exceptional is that we can measure the barrier’s permeability while simultaneously mapping morphological changes to the barrier by means of high-resolution time-lapse microscopy.” “This strategy allowed us to almost fully replicate the 3D cell structure found in the human body,” Modena says. To recreate the barrier, the research team took those cell types that naturally make up the blood-brain barrier-microvascular endothelial cells, human astrocytes and human pericytes-and combined them within a single platform. Working under Andreas Hierlemann, Modena and his colleagues spent three and a half years developing the open-microfluidic 3D blood-brain barrier model. If each of these challenges were a bird, Modena’s platform would be the proverbial stone that kills them all. There are also dynamic in-vitro models that simulate flow conditions in the body, but the catch here is that the pumps they require make the experimental setup rather complicated.Īlongside all these challenges, there is the problem of measurement: it is all but impossible to take high-resolution images of structural changes to the blood-brain barrier in real time while also measuring the barrier’s electrical resistance, both of which reflect barrier compactness and tightness. In other words, the cells are floating in a suspension that is not moving, which implies that fluid flow or the shear stress the cells are exposed to in the body are not considered. This approach fails to represent the complex structure of the human system and disregards, for instance, the communication between the various cell types.įurthermore, many of these models are static. The problem with many in-vitro models is that they recreate the blood-brain barrier in a relatively simplified way using blood-vessel-wall cells (endothelial cells). Cell–cell communication largely overlooked An alternative is to base experiments on human cells that have been cultivated in the laboratory. Moreover, there are some critics, who question the basic validity of animal testing. In addition to such experiments being relatively expensive, animal cells may provide only part of the picture of what is going on in a human body. To discover how this barrier works, scientists often conduct experiments on live animals. This wall is also important from a medical perspective, because many diseases of the central nervous system are linked to an injury to the blood-brain barrier.
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“So what we are trying to understand is how to maintain this wall, break through it and repair it again.”
Sometimes, such holes can actually be useful, for example, for supplying the brain with urgently needed medicine. If he were to explain his research on the blood-brain barrier-the wall that protects our central nervous system from harmful substances in the blood stream-to an 11-year-old, he would say, “This wall is important, because it stops the bad guys from getting into the brain.” If the brain is damaged or sick, he says, holes can appear in the wall. Mario Modena is a postdoc working in the Bio Engineering Laboratory at ETH Zurich. Researchers at ETH Zurich have developed a more realistic model that can also be used to better explore new treatments for brain tumors. Up to now, the use of models to research the barrier that separates the circulatory from the nervous system has proven to be either limited or extremely complicated. Summary: Researchers have created a new model of the blood-brain barrier that can mimic fluid flow to and from the brain.
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