Multiple sclerosis: Inflammation of the brain barrier may play a role

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Inflammation of the meninges, the protective barrier of the brain, may contribute to the development of multiple sclerosis. Image credit: Dimitri Otis/Getty Images
  • New research suggests that inflammation in the meningesprotective barrier of the brain, may extend into the gray matter and contribute to the development of progressive multiple sclerosis (MS).
  • The researchers used innovative techniques to demonstrate a gradient of immune genes and inflammation markers that extends from the meninges to adjacent brain tissue in mice.
  • While the study sheds light on the mechanisms of brain damage in MS, limitations in spatial resolution and the use of a mouse model demonstrate that further investigations using human samples are needed.

A new study whose results appear in and Life as a journal Preprint used innovative techniques to demonstrate a gradient of immune genes and markers of inflammation that extends from the meninges to adjacent brain tissue in mice.

THE meninges they are a set of three layers of membranes that surround and protect the brain and spinal cord.

These membranes, known as the dura mater, arachnoid mater, and pia mater, are intended to protect and secure the brain, as well as provide a structural framework for the blood vessels, nerves, lymph vessels, and cerebrospinal fluid that envelop the central nervous system.

Inflammation that occurs within the meninges is seen in all forms of multiple sclerosis (MS).

Mounting evidence indicates that this inflammation plays a crucial role in disease progress, including loss of protective covering over nerves (demyelination), loss of newly developed nerve extensions (neuritis), and a reduction in gray matter volume.

Gray matter damage is associated with debilitating symptoms of MS, such as cognitive impairment and depression. Meningeal inflammation appears to be a crucial contributing factor to cortical gray matter pathology.

In this study, the researchers investigated gene expression patterns within the meninges and nearby gray matter, focusing on maintaining contextual information regarding the placement of these cells within the brain.

They used a technique called spatial transcriptomics, which involves measuring the gene activity pattern within a tissue and reconstructing the original gene activity pattern at its specific location.

First, they assessed gene activity in the inflamed meninges of mice with an MS-like condition and compared it to gene expression in the meninges of healthy mice. They then looked at gene expression in the surrounding gray matter of both sets of mice.

As expected, they observed increased expression (upregulation) of immune cell-associated genes, infiltration of immune cells and activation of specific immune cells in the brain known as microglia.

To gain insights into the proximity of this gene activity to the meningeal region, the researchers analyzed gene expression patterns along a pathway from the meninges to the thalamus, finding that all groups of genes showed reduced activity as distance from the inflamed meningeal region increased.

However, some genes showed a more gradual decline, particularly those involved in immune processes such as antigen processing and presentation.

This suggests that some upregulated pro-inflammatory genes had extended from the meningeal region of the brain into the gray matter.

A limitation of this study is that the spatial resolution may not be precise enough to accurately distinguish between the meninges and adjacent gray matter.

Furthermore, although the researchers used a mouse model that mimics several pathological aspects of MS, it does not fully replicate the human disease.

Also, the analysis did not take into account the different stages of MS development or the different types of the condition that occur in humans.

However, the authors suggest that their findings could serve as a basis for future investigations using human samples.

Dr. Pavan Bhargava, associate professor of neurology in the Division of Neuroimmunology and Neurological Infections at Johns Hopkins University, Baltimore, MD, and senior author of the paper, said Medical News Today that, while inflammation in the coverings of the brain has been linked to more severe disease and more damage in the brains of people with MS, questions remain as to whether the inflammation causes the damage or is simply a response to the damage occurring in the brain.

We used a technique called spatial transcriptomics which allows us to evaluate [the] expression of genes on a slide that provides critical information about where different genes are expressed in the brain and surrounding tissue, explained Dr. Bhargava.

Using a mouse model of MS we identified areas of inflammation in the linings of the brain and noted that some inflammatory gene signatures showed penetration into adjacent brain tissue while others did not. This suggests that inflammation in the linings of the brain is impacting the brain and identifies potential targets for treatment.

Dr. Pavan Bhargava

Nancy Mitchell, a registered nurse and assistant at the Assisted Living Center who was not involved in the research, pointed out that, as with most autoimmune diseases, the onset of multiple sclerosis is linked to a certain level of inflammation in the body—in this case, the nervous system.

This study highlights the relationship between inflammation of the blood-brain barrier and the progression of this disease, Mitchell explained.

The parenchyma is the site of the brain associated with cognitive function. It is very likely that inflammation that can be caused by an immune attack or related damage could cause impaired nerve function and promote MS, he speculated.

Dr Bhargava stressed that the research, if its findings are confirmed by further studies, could have some implications for the development of new treatments for MS.

So far, the study has identified potential targets for reducing the impact of meningeal inflammation on underlying brain tissue, which, if validated in human tissue, could be the basis for evaluating drugs targeting these pathways in people with MS, he told us.

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