The 2017-2018 flu season has been really bad, due in large part to the exceptionally slippery H3N2 influenza strain, this flu season’s dominant strain, which is much better at sneaking around the protection offered by vaccines than other flu strains. Earlier this month, officials from the Centers for Disease Control and Prevention announced that the flu season was far from over, and on Friday, the CDC announced that the number of pediatric deaths had risen to 97.

And while this ravaging flu season has a lot of people focused on the short-term effects of influenza infections, researchers are also concerned about what long-term impacts the flu could have on the brain. A new mouse brain study suggests that the neurological consequences of the flu could be more long-lived than previously understood.

In a paper published Monday in the journal JNeurosci, researchers report that female mice who got the flu showed neurological inflammation symptoms, even many days after the acute phase of the illness had passed. We know that the flu can affect your brain, but this shows that those effects could last well after the worst of the infection.

Allen Brain Institute Observatory Mouse
Researchers infected mice with the flu and dissected their brains. They found physical changes even after the infection had subsided.

To conduct this research, the team of U.S. and German scientists infected mice with one of three strains of influenza A (H1N1, H3N2, and H7N7) and then performed cognitive tests — mazes — on the mice. Thirty days after the infection had subsided, the researchers found that the H3N2 and H7N7 mice had trouble navigating these mazes, suggesting they had impaired memory function even though they were no longer showing acute symptoms of the flu.

The researchers dissected the mouse brains and found that these behavioral deficits were accompanied by structural changes in the brains. Specifically, the researchers observed inflammation in the hippocampus, the area of the brain associated with working memory. After 120 days, though, the brain structure and behavior had returned to levels similar to that of a control group.

While the results of this study should be considered preliminary since it was conducted on mice and not humans, mice and humans have brains that function quite similarly, so it’s possible that this research can give us some insight into how the flu affects people’s brains can continue to be affected by the flu, even after they seem to have gotten better. More research will reveal just how much we experience the flu as mice do.

Abstract: Acute influenza infection has been reported to be associated with neurological symptoms. However, the long-term consequences for the CNS of an infection with neurotropic but also with non-neurotropic influenza A virus (IAV) variants remain elusive. We can show that spine loss in the hippocampus after infection with neurotropic H7N7 (rSC35M) as well as non-neurotropic H3N2 (maHK68) in female C57BL/6 mice persists well beyond the acute phase of the disease. While spine number was significantly reduced 30 days post infection (pi) with H7N7 or H3N2, full recovery could only be observed much later at 120 days pi. Notably, infection with H1N1 virus which was shown previously to acutely affect spine number and hippocampus-dependent learning had no significant long-term effects. Spine loss was associated with an increase in the number of activated microglia, reduced long-term potentiation in the hippocampus, and an impairment in spatial memory formation indicating that IAV associated inflammation induced functional and structural alterations in hippocampal networks. Transcriptome analyses revealed regulation of many inflammatory as well as neuron- and glia-specific genes in H3N2 and H7N7 infected mice at day 18 and in H7N7 infected mice at day 30 pi that related to the structural and functional alterations. Our data provide evidence that neuroinflammation induced by neurotropic H7N7 and infection of the lung with a non-neurotropic H3N2 IAV result in long-term impairments in the CNS. IAV infection in humans may therefore not only lead to short-term responses in infected organs but also trigger neuroinflammation and associated chronic alterations in the CNS.