Blood-Brain Barrier May Present Treatment Target in Multiple Sclerosis


Targeting specific transportation system across the damaged blood-brain barrier could halt MS disease progression.

Vascular function in multiple sclerosis (MS)—specifically the blood-brain barrier—could be a target for treatment in the future, according to a recent report.

Researchers from the University of Illinois at Chicago College of Medicine used the blood-brain barriers of mice in order to explore how Th1 and Th17 immune cells access the neurons and cause MS. The researchers marked blood vessel endothelial cell tight junctions with a florescent protein.

The tight junctions are the hubs of endothelial cells that prevent chemicals, harmful microbes, and other cells from gaining access to the brain and spine via the blood-brain barrier. The investigators were then able to observe what affect the tight junctions had on mouse subjects’ form of MS.

In blood vessels surrounding other organs in the body, the endothelial cells do not form a tight junction. Instead, they are more loosely bound and permit the flow and exchange of molecules and cells from the bloodstream into the tissues, and vice versa, the study authors explained.

The researchers learned that in the early onset of the disease, tight junctions became significantly deteriorated in the presence of Th17 cells. After a period of about 3 days in the disease’s process, Th1 cells were attacking myelin and neurons. However, the difference with these lymphocytes was that the Th1 cells were not passing through the tight junctions, but Th17 cells could.

The Th1 cells were still able to reach the myelin and neurons through the caveolae, a specialized cell membrane structure. The caveolae monitors the passage of material through cell walls, according to the study.

“[The findings] suggest that protecting tight junctions could be helpful in preventing the development of new disease,” study author Dr. Sarah Lutz told MD Magazine. “But patients rarely come to their doctor for prophylactic treatment — more commonly, we treat our patients after they are already sick.”

The researchers also observed mice bred to lack caveolae in their study, learning that there were almost no Th1 cells in the brains or spinal cords. Because of this, the study authors concluded that caveolae on endothelial cells are vital to getting Th1 cells through the blood-brain barrier.

“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,” the study’s senior author, Dritan Agalliu, PhD, from Columbia University, told MD Magazine.

Many MS therapies now target the immune system, Agalliu said.

“Though that may help alleviate symptoms, it won’t stop disease progression, because other inflammatory factors will still enter the brain through the barrier, triggering a cascade of pathologies that are independent of T cells,” Agalliu said.

Lutz and Agalliu both said that the study suggests that there is a need to focus on vascular function in combination with immune function to effectively treat MS, as well as a variety of other neurological diseases, in the future.

The paper, titled “Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation,” was published in Cell Reports.

A press release regarding the study was made available.

This article was originally published by MD Magazine.

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