Researchers are examining the importance of the blood-brain barrier in terms of multiple sclerosis.
In multiple sclerosis, immune cells break through the blood-brain barrier and attack nerve cells.
New video footage is now revealing the paths those cells use to breach this barrier—some slip through weak spots in the barrier, while others travel in tiny particles across the cells that make up this barrier—and giving scientists ideas about how to stop the cells from entering the brain.
In the healthy central nervous system, the blood-brain barrier is constructed from a tightly packed layer of endothelial cells that line blood vessels, keeping viruses and toxins that are circulating in the bloodstream from slipping into the brain and/or spinal cord. In people with MS, this barrier becomes more porous, and immune cells slip past and attack the myelin that surrounds nerve cells.
Using new microscopy techniques that allow researchers to visualize contacts between endothelial cells in the spinal cord of living mice, Dritan Agalliu, PhD, assistant professor of pathology & cell biology (in neurology and pharmacology) at Columbia, examined the contact points between the barrier’s endothelial cells in a strain of mice with a condition similar to MS.
“The first thing we found is that contacts between endothelial cells—the so-called tight junctions—break down very early in the course of MS, before we see any clinical manifestations,” said Dr. Agalliu, whose findings were reported in Cell Reports. “This is the first in vivo evidence that blood-brain barrier dysfunction is an early and prominent feature of the disease.”
Dr. Agalliu also saw that immune cells were able to exploit loose junctions to cross the barrier and enter the brain. One type of immune cell, Th17, slips through the loosened cell junctions, while another immune cell, Th1, is transported across the endothelial cell via small vesicles and released into the central nervous system. In mice lacking these specialized vesicles, few Th1 cells are found in the central nervous system of mice with MS, reducing their symptoms.
“Tightening loose junctions and targeting this transportation system across the damaged blood-brain barrier could potentially prevent both types of immune cells from entering the nervous system and reduce or halt disease progression,” Dr. Agalliu said.
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