How do blood vessels protect the brain during inflammation?

Recently, researchers at the University of British Columbia have found how blood vessels protect the brain during inflammation. This finding may lead to new treatments for neurodegenrative diseases such as stroke, multiple sclerosis.

The brain and spinal cord are made up of neurons, which have different functions, such as controlling movement, processing sensory information, and making decisions. Cells in the brain and spinal cord are generally not regenerated, so excessive damage can be devastating and irreversible. Neurodegenerative diseases are caused by the loss of neurons or myelin, which deteriorate over time to cause dysfunction. Neurodegenerative diseases can be divided into two categories: one that affects exercise, like amyotrophic lateral sclerosis; one that damages memory and related dementia, for instance, Alzheimer's disease.

In their article published in the Proceedings of the National Academy of Sciences, the researchers expounded a protein in the vessels called podocalyxin, plays an important role in preventing the harmful blood components from entering into the brain during inflammation, in response to infections or damage.

This is the first time that this protein has been shown to be critical for the integrity of the blood-brain barrier. The discovery marks scientists first understand the function of podocalyxin in the blood-brain barrier. It is a membrane that separates the brain from the blood circulation of other parts of the body, which is crucial for maintaining healthy brain function. Podocalyxin functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. However, it acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands and increasing the rate of migration and cell-cell contacts in an integrin-dependent manner.

This breakdown of the barriers is common in neurodegenerative diseases and causes disease symptoms.

In order to conduct the research, the researchers analyzed the effect of the loss of podocalyxin in human endothelial cells and inflammatory mouse models. They demonstrated that endothelial cells which supply the inner tube of blood vessels, need podocalyxin to strengthen the blood vessels.

Endothelial cells, also known as vascular endothelial cells, usually refer to a single layer of flattened epithelium lining the inner surface of the heart, blood vessels, and lymphatic vessels, which forms the inner tube of the blood vessels. During inflammation, endothelial cells express high adhesion molecules and interact with leukocyte surface adhesion molecules in the bloodstream, thereby mediating leukocytes crossing the vessel wall. They have tissues that devour foreign bodies, bacteria, necrosis and senescent, and are also involved in immune function, such as inflammation.

The researchers hope their findings will lead to the development of new drugs and treatments to prevent the breakdown of the blood-brain barrier.

A major obstacle to treating neurodegenerative diseases is that most drugs can not cross the blood-brain barrier. The researchers believe that if they can induce the blood-brain barrier to open instantaneously, it could allow the drug to enter the brain and to better exert their effects. So they will further study and explore how to manipulate podocalyxin to control the open blood-brain barrier.