This is the fourth article in a series that focuses on cognitive disorder and inflammation. The first component can be read here, the moment can be read here and the third here. For more information on inflammation and Covid-19, visit my website: www. williamhaseltine. com
In previous episodes of this series, we looked at new studies suggesting that even a mild SARS-CoV-2 infection can affect cognitive function. The first step in this chain of events occurs when the virus triggers an intense inflammatory reaction that reaches the brain. Once there, inflammation triggers the reactivity of microglial cells, the resident immune cells of the central nervous system formula, which produce even more inflammation and interfere with the overall functioning of vital cells, adding oligodendrocytes and neural precursor cells (Figure 1).
But since all of this happens because of inflammation, which we reveal in a number of infections or injuries, wouldn’t we expect to see something similar in other viral diseases?As part of their research, Fernández-Castañeda et al. they asked the same question themselves. In search of an answer, they turned to the flu.
Like COVID-19, the flu has also been linked to cognitive and neurological disorders. And like SARS-CoV-2, the flu is rarely neuroinvasive, even though any of the viruses can directly infect the brain, like many other viruses, it turns out to occur only rarely. It may be that influenza causes cognitive impairment through a mechanism similar to that of SARS-CoV-2.
To find out, the researchers exposed an organization of mice to the H1N1 strain of influenza. This strain is not neuroinvasive in mouse models, the infection is limited to the trachea and lungs. To keep things in line with their Covid-19 experiments, the researchers made sure the mice only had mild flu, as evidenced by minimal illness behaviors and minimal weight loss.
Despite a largely benign disease, the mice showed symptoms of superior inflammation, with a noticeable buildup in cytokine and chemokine levels. The researchers discovered them in blood and cerebrospinal fluid, indicating that inflammation had made its way into the nervous system.
The profile of influenza-induced cytokines largely mirrored that of mice with mild Covid-19 breathing (Figure 2). In either case, cc-pattern chemokine ligand 11 (CCL11) is provided in the cerebrospinal fluid seven days to seven weeks after infection. In fact, grades CCL11 were higher at seven weeks than at seven days.
This means that the first component of the mechanism behind cognitive decline after Covid-19, the peripheral inflammation that triggers neuroinflammation, also provides a flu infection. What about the remaining items?
In the context of Covid-19, high levels of CCL11 were related to the accumulation and reactivity of microglial cells. By reading the white matter of mice exposed to influenza, the team of researchers discovered a similar accumulation in microglial reactivity; the total number of microglial cells remained the same in the influenza and control organizations, the number of activated microglial cells was particularly higher in the recovering mice.
Accumulation in activated microglial cells accompanied damage to oligodendrocytes and a decrease in the production of new neurons in the hippocampus, called neurogenesis. Exactly the same pathology observed in mice with Covid-19.
Neurogenesis in the hippocampus deteriorated as early as seven days after influenza infection, and this persisted for at least seven weeks after infection. Microglial cells in this region remained reactive at all times. recovery in oligodendrocyte counts. Although there was a marked decrease seven days after infection, the oligodendrocyte population had normalized within seven weeks. This correlates with stable relief in microglial reactivity over the same period.
Therefore, they share the same underlying mechanism, the cognitive disorder caused by influenza differs from that caused by SARS-CoV-2; Or they cause a lasting decrease in neurogenesis in the hippocampus, but only SARS-CoV-2 causes more lasting damage in oligodendrocyte production.
Aftermath
The effects of viral infections can worsen over several weeks, months, and even years after infection. When it comes to cognitive decline, those findings identify systemic inflammation, which ultimately manifests itself in the brain, as a learning factor.
Not all viruses have the same effect because not all cause the same amount of inflammation. This is true even for other strains of the same virus, although the flu in general is not known to cause neurological problems. the strain that caused the Spanish flu pandemic of 1918 led to a strong accumulation of Parkinson’s disease. As the virulence of the strain slowly decreased, it followed the intensity of the inflammatory reaction, as did the frequency of neurological and cognitive symptoms. It will be a matter of time before some other virus with such a capacity appears.
This is evident with SARS-CoV-2, which has been characterized by the strength of the inflammatory reaction it triggers; in a sense, this is a feature of the virus. This manifests itself through cytokine storms, hypercoagulation, and disturbing levels of cytokines and chemokines circulating in the blood and cerebrospinal fluid.
While we can expect slight differences between the variants, the common theme is long-term cognitive and functional damage, some of which seem and others may not appear until much later.