The blood-brain barrier (BBB) is an essential feature that protects the brain from potentially harmful substances in the blood; however, when there is a disruption in the BBB — such as after a stroke — brain-damaging substances may be allowed to pass into the brain.
Even when working properly, research suggests that the blood-brain barrier may hinder the transport of needed medications to the brain.
So scientists at Karolinska Institutet have discovered a potential solution to these problems and hope that their findings will eventually lead to new options in treating diseases like Alzhemer’s and stroke.
The blood-brain barrier consists of high-density cells that act as a protective wall between the blood and the brain and spinal cord. In other organs, the capillary walls let in certain substances found in the blood—including the plasma proteins albumin and immunoglobulin — into the surrounding tissue.
In the brain, however, this pathway is closed off. This is crucial for several reasons, one being that the plasma proteins are damaging to nerve cells.
Lately, scientists have discussed capillary permeability in the brain as a possible significant factor in neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and ALS. They have discovered that a connective tissue cell called a pericyte is key to the BBB.
“Our new results show that the blood-brain barrier is regulated by pericytes, and can be opened in a way that allows the passage of molecules of different sizes while keeping the brain’s basic functions operating properly,” says Christer Betsholtz, professor of vascular biology at the Department of Medical Biochemistry and leader of the study.
“Our new knowledge of how the BBB is regulated could be used in two ways,” says Prof. Betsholtz. “To protect the brain under conditions such as stroke and inflammation that lead to the opening of the BBB and the release of neurodamaging substances, and to open the barrier temporarily to allow the transport of drugs against neurodegenerative and other diseases of the brain.”
In the study, Prof. Betsholtz and his team demonstrate how this would be possible. The pericytes normally maintain the barrier actions through an unknown molecular mechanism; yet, in their absence, a special transport process called transcytosis opens a pathway through the capillary walls so that molecules of varying sizes, including large plasma proteins, can pass from the blood into the brain.
The pericytes also regulate astrocytes, which are brain cells that contribute to the BBB through special extensions called ‘end-feet’ which take over the capillaries and regulate the flow of water and ions.
“Another interesting find is that the cancer drug Imatinib, which inhibits certain signal proteins for cell growth, has a similar effect in the presence of pericytes in that they also close the capillary wall transport paths,” says Prof. Betsholtz.
Scientists hope these findings will offer new options in treating diseases associated with the BBB.
This study can be found in the journal Nature.
Source: Karolinska Institutet