Even mild Covid-19 can cause persistent brain fog (part 2)

This is part 3 of a series focusing on cognitive impairment and inflammation.read the first article hereand the second can read hereFor more articles on inflammation and Covid-19, visit my website. www. williamhaseltine.com

For many people, encountering Covid-19 results in lingering cognitive symptoms commonly referred to as “brain fog.” And in some cases, these symptoms can persist for months.a new research I will explain why and how this is happening.

and previous article, which outlined some of the researchers’ findings. In brief summary, SARS-CoV-2 infection can cause severe inflammation and can enter the central nervous system, including the brain, through a series of ‘signaling cascades’. Once there, inflammation triggers the activation of immune cells called microglia, which lead to chaos and additional inflammation that disrupts the brain’s sensitive microenvironment. even can cause this domino effect.

But how exactly does microglial reactivity damage the brain, and how does this damage contribute to cognitive impairment?

Fernández-Castañeda et al. suggest two main mechanisms of injury: the first is the decreased production of new neurons in the brain’s hippocampus, known as neurogenesis. Second is the loss of oligodendrocytes, which produce the myelin that keeps neuronal communication smooth. In both scenarios, symptoms similar to brain fog are to be expected. Associated with neurogenesis disorders, a small signaling protein called CC-motif chemokine 11 (CCL11), already associated with cognitive decline in the elderly, was identified as a major cause.

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neurogenesis

The hippocampus is a brain structure closely involved in both learning and memory formation. Neurogenesis is speculated to be the process by which old or damaged neurons are replaced by new ones, helping hippocampal function to function smoothly.

Generation of new neurons is measured by quantifying Doublecortin-positive cells. All cells, with the exception of bacterial and archaeal cells, contain a scaffold-like structure known as the cytoskeleton composed of interlinked protein filaments. This gives the cells shape and maintains their internal organization. Microtubules are a type of filament. In neuronal-forming cells and immature neurons, the protein doublecortin (DCX) helps regulate microtubule formation. This is most often seen during embryonic development, when neurons in the cortical structures of the brain are just forming. However, it has also been observed in the hippocampus of certain adult mammals, including humans and various animals. It is thought to indicate continued formation. Therefore, measuring the level of doublecortin in the brain has become a stand-in for measuring the amount of cells destined to become neurons.

Fernández-Castañeda and colleagues studied the hippocampus of mice infected with SARS-CoV-2 and found that the amount of doublecortin-expressing cells was greatly reduced, thus significantly reducing the formation of new neurons. Did. This was pronounced 7 days post-infection and remained so until 7 weeks post-infection. There was also a clear inverse correlation between neurogenesis and microglial reactivity. The higher the number of reactive microglial cells, the lower the number of new neurons.

To identify the driving force behind hippocampal neurogenesis atrophy, an expert group turned to the chemokine CCL11. Although it is only one of many signaling molecules released as part of the inflammatory response, it is found at particularly high levels in the cerebrospinal fluid of mice that have recovered from Covid-19.Also before linked For cognitive decline due to aging.

Indeed, healthy mice injected with CCL11 showed increased numbers of activated microglial cells in the brain. Further implicating chemokines, the increase was specifically localized to hippocampal white matter, with no reactivity in cortical or other subcortical white matter. Microglial activation was immediately accompanied by a decline in neurogenesis, confirming the researchers’ hunch and confirming that CCL11 was the prime suspect.

Inspired by this finding, the researchers also investigated whether CCL11 might be associated with the development of cognitive symptoms in long-covid patients. We studied blood samples from long-term Covid patients and compared them with blood samples from patients without cognitive symptoms. is shown.

Important caveat: The differentiation of stem cells into new functional neurons in the adult hippocampus continues to be a point of vigorous debate. There is a growing body of research supporting that possibility, but it is far from a consensus. This does not mean that microglial cell activation and inflammation are not important factors in post-Covid-19 cognitive dysfunction, but they may be causing damage through different mechanisms. This means that we must accept the fact that

Oligodendrocyte and myelin loss

One alternative explanation is the loss of oligodendrocytes in response to activated microglial cells.

Main function Oligodendrocyte production is the production of myelin that tightly wraps around the axon. Axons are the “wires” of the central nervous system, allowing the transmission of information in the form of electrical impulses. Myelin serves to insulate and protect these axons and helps increase the speed at which information is transmitted.

Researchers found that hyperactivation of microglial cells after Covid-19 correlated with a marked loss of mature oligodendrocytes in subcortical white matter. In infected mice, he lost up to one-third of his oligodendrocytes within 7 days of the first infection, and this persisted for a long time. Weeks after virus elimination. As expected, oligodendrocyte depletion was also accompanied by myelin loss. Again, this continued for several weeks after infection.

speak in meeting Speaking about Long Covid hosted by the Global Virus Network, Stanford neuroscientist Michelle Monje, PhD, one of the study’s senior authors, said: It alters the timing, altering the synchronization and coordination of nerve impulse conduction. This slows cognitive processing time, makes multitasking difficult, reduces attention, and impairs learning and memory. Many of these symptoms are what people experience after cancer treatment and her Covid-19. ”

This is reflected in data for demyelinating diseases such as: multiple sclerosis From data on demyelination and cognitive decline Year.

implication

Work by Fernández-Castañeda et al. provides new insight into one potential cause of post-Covid-19 cognitive impairment. Importantly, their findings suggest that SARS-CoV-2 does not even need to enter the central nervous system or infect the brain directly, just stimulating an inflammatory response can cause permanent damage. suggests that there is a This can occur even after mild Covid-19, when infection is limited to the trachea and lungs.

But there is good news. The resulting damage to myelin and loss of neurogenesis is likely reversible. Based on evidence from, researchers believe that blocking inflammation in the brain should restore the production of myelin and neurons. Targeted cytokine-specific anti-inflammatory strategies are not yet available, but it is only a matter of time.