Study offers insights into lesion formation in MS

February 28, 2024
A new study investigated whether microglia nodules represent the first stage of multiple sclerosis lesion formation. Researchers found that microglia nodules are linked to more severe MS pathology. They hope their findings will result in new therapeutic targets to stop MS progression.

MS is the result of the immune system mistakenly attacking the brain and the spinal cord, causing tissue damage throughout. But the underlying mechanism of lesion formation is still not entirely understood. 

People with MS have clusters, or nodules, of a specific type of immune cell known as microglia. Microglia nodules are linked to brain pathology. Microglia remove dead, redundant, or and potentially dangerous particles from the central nervous system. In the normal appearing white matter, where no other pathology is evident, clusters of microglia are already visible. Whether these nodules are related to the progression of MS was still unclear, as they appear in almost all brain disorders as well as the aging brain.

To learn more about the role of nodules in MS patients, researchers at the Netherlands Institute for Neuroscience investigated the pathology of MS in brain donors at the Netherlands Brain Bank in samples with and without nodules. These samples offered insights into the severity of the MS pathology of the patients’ level of inflammation. They found that patients with these nodules have a worsened pathology: they have more lesions and these lesions are more active.

But do the nodules play a role in the formation of lesions in MS or are they a result of something else? For this question, researchers compared their genetic profile to the nodules found in a completely different medical condition: stroke. This is because nodules in brain tissue from people who suffered from a stroke will not lead to lesion formation. Interestingly, the samples from MS patients showed vastly different genes to the nodules in stroke patients.

The researchers recognized many of the genes in the MS nodules because they are’re also expressed in the active lesions. They could almost be described as mini-lesions. The MS nodules were activated by lymphocytes, which were not found in the stroke tissue.

When researchers took a closer look, they found the nodules were absorbing and processing oxidized lipids, which is known to result in activation of these microglia. When researchers looked at the axons surrounded by the nodules at high resolution, they found they were linkedlinkage to partially demyelinated axons. These nodules likely arose to clean up the oxidized myelin. Nodules that are activated by both the lymphocytes and these oxidized lipids may become very inflammatory, causing more damage to the surrounding tissue, surrounding them, leading to a sort of downward spiral.

The researchers noted the need to explore the relationship between all the inflammatory components in the lab so they can understand exactly what leads to these early signs of breakdown. After that, they can consider which steps can be removed from this process to avoid the development of new lesions altogether.

The findings were published in the journal Nature Communications.

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