Developing a more comprehensive understanding of the interactions between the brain, blood vessels, and the immune system holds great promise for unlocking new ways to treat neurological diseases like multiple sclerosis (MS), a team of researchers argued in a new commentary paper. “Interactions between the brain, blood vessels, and…

EHP-101, an experimental treatment being clinically tested for multiple sclerosis (MS), activates a cellular signaling pathway that promotes blood vessel development and reduces inflammation following brain injury, a new study shows. The findings continue to support the use of EHP-101 in MS, a condition marked by excess inflammation and…

Treatment with interferon beta (IFN-beta) — a disease-modifying therapy that lowers inflammation in multiple sclerosis (MS) — was found to restore the ability of blood vessels in the brain to dilate following a stimulus. A new study suggests that this ability, called cerebrovascular reactivity or CVR, is reduced…

Oligodendrocyte precursor cells (OPCs), the cells responsible for myelin production, are unable to migrate into sites of myelin loss in the brain. These cells then cluster and disrupt the blood-brain barrier (BBB), triggering an inflammatory process in the early stages of multiple sclerosis (MS), a study shows. The study, “Aberrant oligodendroglial–vascular interactions disrupt the blood–brain barrier, triggering CNS inflammation,” was published in the journal Nature Neuroscience. MS is an autoimmune disease characterized by the loss of myelin (demyelination) — the fat-rich substance that protects nerve fibers — which leads to neurodegeneration. Along with loss of myelin, researchers have observed that the blood-brain barrier — a highly selective membrane that shields the central nervous system with its cerebrospinal fluid from the general blood circulation — breaks down in the initial stages of disease. A team led by researchers at the University of California, San Francisco, have now discovered that OPCs are involved in the disruption of the blood-brain barrier in MS, according to a press release from the National MS Society, which funded the study. Oligodendrocytes are myelin-producing cells and are responsible for myelinating the nerve cells’ axons — a single oligodendrocyte is capable of myelinating multiple axons. Mature myelin-producing oligodendrocytes develop from more immature, stem cell-like OPCs. In a normal brain, upon myelin loss, OPCs are called into action and travel into the damage site where they mature and generate myelin-producing oligodendrocytes. In this study, the researchers found that OPCs in MS form clusters in blood vessels of the brain-blood barrier, having lost the ability to detach from these vessels and migrate to injury sites. In an animal model of MS, they saw that OPC aggregates altered the location of other cells — called astrocytes — in a competition for space, and contributed to the disruption of blood vessels. Astrocytes are a group of star-shaped cells, belonging to the group of glial cells, that provide neurons with energy, and work as a platform to clean up their waste. They also have other functions within the brain, such as regulating blood flow and inflammation. The team also observed that OPC aggregates trigger an immune inflammatory response, shown by a large number of microglia (the central nervous system immune cells) and immune cells called macrophages around these cell clusters. “We find in several MS cases, in lesion areas with active inflammation, that OPCs can be found clustered on vasculature, representing a defect in single cell perivascular migration and inability to detach from blood vessels,” the researchers wrote. Further molecular analysis revealed that OPCs have high levels of Wnt signaling, and elevated secretion of Wif1 factor to the extracellular space that could explain why OPCs accumulate and destroy the blood-brain barrier. The WiF1 factor is actually a negative regulator of Wnt signaling that is essential for the maintenance of the blood-brain barrier structure. This factor competes with Wnt ligands, and affects the integrity of cellular junctions, making the blood-brain barrier more fragile and permeable. "Evidence for this defective oligodendroglial–vascular interaction in MS suggests that aberrant OPC perivascular migration not only impairs their lesion recruitment but can also act as a disease perpetuator via disruption of the BBB,” the researchers wrote. They suggested that more studies are needed to better understand the interactions between blood vessels and oligodendrocytes, which could help identify new therapeutic targets for promoting myelin repair in MS.

Endothelial cells, those lining the inside of small blood vessels, promote clearance of myelin debris — a common detrimental outcome of demyelinating diseases such as multiple sclerosis (MS) or spinal cord injury. However, in its path to clear the brain from myelin debris, endothelial cells trigger more damaging mechanisms, promoting…

Liberation therapy was seen to be an ineffective treatment — both in the short and long term — in a Canadian study in people with multiple sclerosis (MS), its researchers reported, advising patients not to assume the procedure’s risks or cost. Lindsay Machan, a radiology professor at the University of British…

To reach tissues infected with foreign agents, neutrophils, the body’s first line of defense, need to travel through vessel walls — and do so by switching on a class of adhesion receptors, called integrins, that bind to other adhesion molecules at the surface of the capillary walls. Now, in a recent paper published…