Cerebrum Summer 2020

To get into the brain or spinal cord, a virus has to essentially invade all the brain’s peripheral defenses like the blood- brain barrier as well as the different immune responses.

exhibit symptoms such as tremors—the kind of movement disorder seen in Parkinson’s. Smeyne wonders if there might be a link between viral infection and this or other forms of neurodegeneration. “We know, for example, that the 1918 flu pandemic killed a lot of people,” he says. “But what a lot of people don’t realize is that starting around 1936 to 1943, there was a dramatic increase in the rate of Parkinson’s disease. It’s the only time, I believe, in history, that the average incidence rate (number of newly diagnosed people at a specific time point) jumped from two to three percent in people over the age of 55. There could be a link between flu infection and later issues.” H1N1, or the swine flu, does not directly infect neurons like its bird counterpart. Yet, studies consistently show that it can lead to a cytokine storm or hyperactive immune response in the brain. When Smeyne and his team gave mice that had recovered from a previous swine flu infection small doses of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a neurotoxin that can mimic Parkinson’s disease, they found that evidence of permanent damage. “The animals that had been infected showed basically a Parkinsonian-type lesion in the (brain’s) substantia nigra. Those who hadn’t been infected showed no effect,” he says. “It suggests that flus or viruses that cause these cytokine storms could prime the brain for later insult. It’s possible that your brain could sustain damage later from the virus you were infected with today.” Understanding Covid-19 and the Brain As more case studies about Covid-19 are published, it is becoming clear that SARS-CoV-2 is a virus with immense

reach. But to date, much of what doctors and scientists have to go on is anecdotal evidence—not hard data. Moving forward, UC neurologist Tyler says, there are many questions that need to be investigated so we can better understand how the novel coronavirus impacts the brain and neurological function. “It’s hard to do research in the middle of a pandemic— doctors are focused on saving lives,” he says. “But these case studies are showing that we better pay attention. Future studies should look carefully at how this virus enters the host, what kind of cells it infects, how it spreads in the body, and what kind of damage it is doing. That’s going to take time.” Pathological studies looking at individuals who have perished from Covid-19 have already started. A small pathological study of 18 patients , published as a letter in the New England Journal of Medicine in June, suggests that most damage occurred due to hypoxia, or a lack of oxygen to the brain. Researchers are also relying organoids, so-called “mini-brains,” to see how the virus may affect the different cells in these three-dimensional, self-organization tissue culture models. Using this approach, researchers from Johns Hopkins University discovered that Covid-19 can both infect and spread across neural tissue —but they cannot say with any certainty that the virus can pass through the blood brain barrier to get into the brain in the first place. While such studies are revealing curious and sometimes contradictory new insights about Covid-19, they are only a first step in a long scientific journey. To more fully understand how this virus affects the nervous system, researchers will need a good animal model and, until a vaccine is developed, a biosafety level 3 laboratory in which to do controlled experiments.


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