Q: What is a blood-brain barrier?
Krishna: The blood-brain barrier (BBB) plays an essential role in protecting the central nervous system from harmful bacteria, toxins, and other blood-borne pathogens.
Composed of a tight row of endothelial cells, the barrier is semipermeable and highly selective. It allows small molecules and nutrients to pass from the blood into the central nervous system, while blocking substances that might cause infection, inflammation, and otherwise disrupt the system's delicate balance.
The blood-brain barrier is not simply a wall that physically blocks harmful molecules from crossing into the central nervous system. Rather, it acts more like a self-regulating filtration system, and its permeability changes based on the properties of the endothelial cells it's made of.
Researchers have earlier established that a cellular trafficking system called transcytosis plays a key role in controlling blood-brain barrier permeability by determining how easily molecules can be transported across it. Now, new research (1) in mice has revealed more details about how this process is regulated.
In this new research, published March 15 in Neuron, the scientists describe a mechanism by which cells in the surrounding environment, or microenvironment, signal to cells that make up the blood-brain barrier. They found that this intercellular communication inhibits transcytosis to keep the barrier less permeable and ensure that molecules cannot easily pass through.

Not only that, but the mechanism offers a potential avenue for manipulating the barrier to make it more or less permeable, the authors of the study say. If the findings are replicated in further animal studies and then in humans, they could point to new ways of treating diseases or delivering medicines into the brain.

Footnotes:

1. Chenghua Gu, Pericyte-to-endothelial cell signaling via vitronectin-integrin regulates blood-CNS barrier, Neuron (2022). DOI: 10.1016/j.neuron.2022.02.017. www.cell.com/neuron/fulltext/S0896-6273(22)00184-2

Researchers may have unlocked the blood-brain barrier

The brain is composed of billions of neurons—vulnerable cells that require a protective environment to function properly. This delicate environment is protected by 400 miles of specialized vasculature designed to limit which substances come into contact with the brain. This blood-brain barrier is essential for protecting the organ from toxins and pathogens. But in the context of neurological disease, the barrier "becomes your worst enemy" as it also blocks the passage of therapeutic drugs. 

(oh, evolution didn't know you would be discovering or developing drugs for these diseases)

For years, it has been the goal of neuroscientists and vascular biologists alike to find the magic bullet for temporarily opening and resealing the barrier for drug administration. Now, a research team has developed an antibody as a tool for opening the blood-brain barrier for a couple of hours at a time, allowing for the delivery of drugs to a diseased brain. The team published its findings in Nature Communications on March 4.

This is the first time scientists have figured out how to control the blood-brain barrier with a molecule.

The development and maintenance of the blood-brain barrier are dependent on what is called the Wnt signaling pathway, which regulates a number of crucial cellular processes. This research team sought to figure out whether this pathway could be modulated to open the barrier "on-demand."

They chose to study a molecule known as Unc5B, an endothelial membrane receptor expressed in the endothelial cells of capillaries. They found that if they knocked out this receptor in mice, they died early in their embryonic development because their vasculature failed to form properly, indicating that it was an important molecule in vascular development. They also discovered that a protein known as Claudin5—which is important for creating the tight junctions between the endothelial cells of the blood-brain barrier—was also significantly reduced. This made the team realize that the receptor could be important in maintaining this barrier.

There was previously no known link between Unc5B and the Wnt signaling pathway. Through this new study, the team figured out that the Unc5B receptor controls the pathway, functioning as an upstream regulator.

Because the bbb blocks entry to all but a tiny subset of small molecules, neurological conditions such as Alzheimer's, multiple sclerosis, brain tumors, and depression are exceedingly difficult to treat. Having control over the barrier will be helpful for future drug delivery ventures.

Kevin Boyé et al, Endothelial Unc5B controls blood-brain barrier integrity, Nature Communications (2022). DOI: 10.1038/s41467-022-28785-9