Infections can significantly impair the functioning of our brain

Why did so many neurological symptoms appear after the 1918 flu pandemic? What is the explanation for the neuronal damage found in patients with relapsing covid-19? Neuroinflammation caused by viral or bacterial infections is more common than we think. And it can damage the brain in the long run.

Inflammasome and the brain

As we age, our cells and tissues lose functionality and this loss of function is associated with known chronic diseases. One of the common denominators of this process is the accumulation of cellular waste, which ultimately causes cell death and, as a result, the incapacity of the organ to which they belong.

Accumulated damage can also lead to cellular senescence, which leads to the release of substances that cause inflammation.

Currently, many research groups are trying to find anti-aging substances that reduce this aging. In this search, they found that activation of the inflammasome, a complex of proteins that promote the release of inflammatory mediators such as interleukins IL-1 and IL-18, is associated with aging and virtually all associated chronic diseases.

Inflammasome activation and release of inflammatory factors are also associated with degenerative processes affecting the central nervous system, leading to cognitive impairment and Alzheimer’s disease.

For all these reasons, inflammation of the central nervous system, known as neuroinflammation, has become an important therapeutic target for the treatment of neurodegenerative diseases.

Causes of neuroinflammation

What causes the inflammasome to activate in some people and not activate in others? It depends on many factors. Some of these are internal, such as damage to mitochondria (cell power plants) or the accumulation of certain metabolites. But it is also activated by external factors, especially pathogenic ones: viruses, bacteria and fungi. In other words, infections can lead to swelling and deterioration of the brain.

The defenses that come to our rescue can further exacerbate the damage. Recent studies show that the invasion of activated cells of the immune system into nervous tissue may also contribute to inflammation and cognitive decline. Added to this is that when activated T-lymphocytes flock to the brain, tau builds up in neurons, another hallmark of Alzheimer’s disease.

In addition, there are certain genetic factors associated with Alzheimer’s disease, such as variations in the cholesterol-transporting protein APOE4, which have recently been associated with a pro-inflammatory profile in endothelial cells. This partly explains the neuroinflammation and increased deposits of beta-amyloid protein around neurons.

Infections, vascular damage and neuroinflammation

A thin layer formed by very flat epithelial cells separates the blood flow within organs. These cells are called vascular endothelium and perform a very important function: they regulate the flow of substances and cells from the blood to the organs.

In the central nervous system, this cell wall, known as the blood-brain barrier, has special characteristics. First, it is made up of endothelial cells, smooth muscle cells, cells called pericytes, connective tissue, and astrocytes. All of them establish tight contacts with each other, controlling the flow of substances and cells into and out of the central nervous system.

The loss of this barrier properties is associated with various neuronal diseases, including stroke, multiple sclerosis, head trauma and its consequences, and neurodegenerative diseases.

It is clear that any agent that causes damage to the vascular endothelium, and especially that which forms the blood-brain barrier, can provoke neuroinflammation and neurodegenerative processes. On the other hand, viral and bacterial infections often cause damage to blood vessels, including cerebral vessels, which leads to accelerated development of atherosclerosis, vascular inflammation (vasculitis) or coagulopathy. This can lead to strokes or strokes in the short term.

But these same infections can also cause inflammation that ultimately activates immune system cells, which in turn enter neural tissue through the damaged blood-brain barrier, causing chronic neuroinflammation and long-term damage.

Another factor to consider is that endothelial damage increases as more years pass, and in addition, it is accelerated in metabolic diseases such as metabolic syndrome. This explains why covid-19 and other infectious diseases appear to be more severe in obese and/or older people.

Can vaccination campaigns prevent neurodegeneration?

Based on what we have just discussed, we can conclude that preventing endothelial damage after infections is necessary to reduce neuroinflammation and, as a result, reduce neuronal damage caused by Alzheimer’s disease and other neurodegenerative diseases.

In fact, several natural compounds such as polyphenols, vitamin C, and even coenzyme Q10 have been proposed to maintain vascular endothelial stability and protect the brain.

But if, in addition, we take into account that vaccines prevent serious symptoms caused by infections and prevent microorganisms from entering the bloodstream, we can assume that vaccines, which began to be introduced mainly in the 1960s or 1970s, could reduce vascular damage leading to neurodegeneration.

Currently, most older people did not participate in these vaccination campaigns as children. So we’ll have to wait another 20 or 30 years to see if diseases like Alzheimer’s or Parkinson’s decrease in the vaccinated population.

If this were confirmed, we might conclude that preventing certain infections and maintaining vascular endothelial health are necessary to reduce the incidence of degenerative diseases, even in the very long term.

Guillermo López Lluch, Professor of Cell Biology. Junior Research Fellow at the Andalusian Center for Developmental Biology. Researcher in the field of metabolism, aging, immune and antioxidant systems, Pablo de Olavide University

This article was originally published on The Conversation. Read the original.