Unresolved inflammation that hinders the brain's ability to repair damaged neurons and grow new ones may be the reason for neurological problems persisting in people who survive West Nile virus brain infection, reports a new study published in Nature Immunology.
A research team at the university also found in their mice test that when the inflammation was reduced by treatment with an arthritis drug, mice's ability to learn and remember remained sharp after West Nile disease, Xinhua reported.
In the test, the researchers injected mice with West Nile virus or saltwater. During the acute infection, the mice received several doses of a chemical compound that tags neural cells as they are formed.
Mice ill with West Nile disease produced fewer neurons and more astrocytes than uninfected mice. Astrocytes normally provide nutrition for neurons, but the ones formed during West Nile infection behaved like immune cells, churning out an inflammatory protein known as IL-1 to fight invading viruses.
When the fight is won, the immune cells departs and the IL-1 levels in the brain should fall. But in mice recovering from West Nile infection, astrocytes continue to produce IL-1 even after the virus is gone.
As IL-1 guides precursor cells down the path toward becoming astrocytes and away from developing into neurons, a vicious cycle emerges: Astrocytes produce IL-1, which leads to more astrocytes while also preventing new neurons from arising.
Hampered by an inability to grow new neurons, the brain fails to repair the neurological damage sustained during infection, the researchers said.
"It's almost like the brain gets caught in a loop that keeps IL-1 levels high and prevents it from repairing itself," said senior author Robyn Klein, a professor of medicine at Washington University School of Medicine in St. Louis.
To break the cycle, Klein and his colleagues infected mice with either West Nile virus or saltwater as a mock infection. Ten days later, they treated both groups of mice with a placebo or with anakinra, an FDA-approved arthritis drug that interferes with IL-1.
After giving the mice a month to recover, they tested the animals' ability to learn and remember by placing them inside a maze. Mice that had been infected with West Nile virus and treated with a placebo took longer to learn the maze than mock-infected mice.
Mice that were infected and treated with the IL-1 blocker learned just as quickly as mock-infected mice, indicating that blocking IL-1 protected the mice from memory problems.
"When we treated the mice during the acute phase with a drug that blocks IL-1 signaling, we prevented the memory disturbance," Klein said. "The cycle gets reversed back: They stop making astrocytes, they start making new neurons, and they repair the damaged connections between neurons."
"This study sheds light on not just post-viral memory disturbances but other types of memory disorders as well," Klein said.
West Nile virus, spread by the bite of a mosquito, can cause fever and sometimes life-threatening brain infections known as West Nile encephalitis.
About half the people who survive the encephalitis are left with permanent neurological problems such as disabling fatigue, weakness, difficulty walking and memory loss. These problems not only persist but often worsen with time.
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.