Repairing the blood-brain barrier 

Summary: Repairing the blood-brain barrier. Scientists found a way to help the brain stay healthy by fixing the blood-brain barrier in mice.

Everyone has the ability to be a bouncer. The repairing blood-brain barrier is like a wall between the blood vessels and the brain. It stops bad things like toxins and germs from getting into the brain and hurting it.

Source: Stanford Medicine

If the person who checks who goes in is not paying attention, someone who could be trouble might get inside and cause different sorts of problems. Cancer cells that cross barriers can turn into tumors. Sometimes, too many white blood cells can get through a barrier in the body and cause multiple sclerosis. This can make it hard for the brain’s nerves to communicate with the rest of the body.

Many brain illnesses are caused by a leaky barrier that controls the flow of blood in the brain. Doctors want to find a way to stop this from happening. Calvin Kuo, a professor of hematology, said this is something doctors have wanted for a long time.

Research and Discovery

Kuo said that there isn’t enough research on ways to fix the repairing blood-brain barrier. Recently, he and his team wrote a paper about a method that could help fix the barrier’s job. Kuo wrote a paper published in Nature Communications on June 2.

Kuo said that they looked at a new type of medicine that can fix a problem with the repairing blood-brain barrier. Before this, there were no medicines made for this purpose.

The scientists started their search by studying WNT signaling. This is how cells communicate and help the body heal wounds. WNT signaling helps keep the barrier that separates the blood from the brain in good condition. It works by helping cells in the walls of the blood vessels in the brain communicate with each other.

Kuo said that there is a lot of information from the past that shows that the WNT signaling pathway is significant in keeping the repairing blood-brain barrier in good condition. We can try a new way to make signaling happen in the blood-brain barrier. We found a special way to activate a receptor called Frizzled.

Researchers are studying a protein called frizzled that starts a pathway (called the WNT pathway) to help treat problems with the blood-brain barrier. They became interested in this when mice with an abnormal frizzled gene had issues with their blood-brain barrier.

How things are created

The researchers looked for a specific molecule that targets cells in the brain’s blood vessels by ignoring other molecules that bind to frizzled protein receptors.

Chris Garcia, who is a professor and scientist, made some new molecules in his lab that could help people feel better. One of these molecules makes something in our cells called the frizzled receptor FZD4 wake up. A group of scientists made a new molecule called L6-F4-2 that can activate a signal in cells called WNT much better than other molecules that do the same thing. They used the ideas of other scientists named Garcia and Kuo.

When Jie Ding, a research scientist, and the team made WNT signaling stronger, they saw that the blood-brain barrier became stronger too.

Making sure the person who checks who can come in is working

The scientists wanted to see what happens when a key molecule called frizzled is gone and if it can be fixed with a new molecule called L6-F4-2. They looked at Norrie disease, which is a genetic problem that makes the barrier between the blood and retina not work well.

The blood-retinal barrier in the eye works like the blood-brain barrier in the brain. Norrie disease affects the way blood vessels grow in the eye, which causes difficulty in their proper development. This causes problems like blood vessels that leak and can lead to blindness.

Norrie disease happens when something goes wrong with the NDP gene. This gene gives instructions to create a protein called Norrin. Norrin is like a key that unlocks a receptor called FZD4 and makes it work properly. The mice in the study have a gene that doesn’t work and a missing key. This makes their barrier leaky and causes them to become blind. The scientists used a substitute called L6-F4-2 to replace the missing Norrin protein.

Norrie disease

When the L6-F4-2 protein was added, the missing Norrin protein was replaced, and the layer of blood in the eyes of the mice was fixed. Scientists found out that the treatment worked because they looked at pictures of the blood vessels and saw that they were tighter and less likely to leak. Scientists found that a certain substance called L6-F4-2 activates a signaling pathway in the blood-brain barrier of mice. This barrier protects a region in the brain that is important for muscle coordination, called the cerebellum. They also observed that this substance replaced another protein called Norrin.

The researchers wanted to look at a stroke that happens to many people. This kind of stroke harms blood vessels and a protective layer in the brain, causing fluid and other things to enter the brain and hurt it. They discovered that L6-F4-2 made strokes less severe and helped mice survive better than mice who did not receive any treatment for their strokes. L6-F4-2 helped fix leaky blood vessels in the brain after a stroke. The mice that received L6-F4-2 treatment lived longer after having a stroke than the mice that did not receive the treatment.

Conclusion

The study found that drugs that activate certain receptors and pathways in mice could help fix the barrier that protects the brain from harmful substances.

Kuo thinks that if we can fix the problem with the blood-brain barrier. They could treat many different diseases that affect the brain, like Alzheimer’s, multiple sclerosis, and brain tumors.

Kuo said that they are working on making new medicines that fix the blood-brain barrier. They want to use a different approach and target than current medicines. They hope this will be the start of making better drugs.