This is the fourth article in a series focusing on cognitive dysfunction and inflammation. The first part can be read here, the second can be read here, and the third, here. For additional writings on inflammation and Covid-19, please see my website: www. williamhaseltine.com
In previous installments of this series, we looked at new research that suggests even mild SARS-CoV-2 infection can impair cognitive function. The first step in this chain of events happens when the virus sets off an intense inflammatory response that eventually reaches the brain. Once there, inflammation triggers reactivity of microglial cells —the resident immune cells of the central nervous system— which produce yet more inflammation and interfere with the normal functioning of important cells, including oligodendrocytes and neural precursor cells (Figure 1).
But given that all of this happens off the back of inflammation, which we experience during any number of infections or injuries, wouldn’t we expect to see something similar unfold in other viral diseases? As part of their research, Fernández-Castañeda et al. asked themselves this same question. In the search for an answer, they turned to influenza.
Like Covid-19, the flu has also been associated with cognitive and neurological issues. And like SARS-CoV-2, influenza is rarely neuroinvasive — even though both viruses can infect the brain directly, as can many other viruses, it seems to happen only infrequently. It could be, then, that influenza causes cognitive issues through a similar mechanism as SARS-CoV-2.
To find out, the researchers exposed a group of mice to the H1N1 strain of influenza. This strain is not neuroinvasive in mouse models, meaning infection is restricted to the trachea and lungs. To further keep things consistent with their Covid-19 experiments, the researchers made sure that the mice suffered only mild flu, as evidenced by minimal sickness behaviors and minimal weight loss.
Despite largely mild illness, the mice showed signs of elevated inflammation, with a noticeable increase in cytokine and chemokine levels. The researchers found these both in the blood as well as in the cerebrospinal fluid, indicating that inflammation had made its way into the central nervous system.
The influenza-induced cytokine profile closely mirrored that of mice with mild respiratory Covid-19 (Figure 2). In both cases, C-C motif chemokine ligand 11 (CCL11) was present in cerebrospinal fluid from seven days all the way to seven weeks after infection. In fact, CCL11 levels were higher at seven weeks than they were at seven days.