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Maternal immune response may render brain vulnerable to injury

by  /  12 November 2017
Small risk: Infections during pregnancy boost autism risk in the child.

vadimguzhva / iStock

Mouse brains exposed to inflammation in the womb become more susceptible to a second challenge, researchers reported today at the 2017 Society for Neuroscience annual meeting in Washington D.C.

When briefly deprived of oxygen, mice exposed to maternal inflammation show higher immune activation and suffer greater brain damage than their unexposed peers.

Studies in people suggest that infections during pregnancy boost autism risk in the child by as much as 37 percent. Mice exposed to inflammation in the womb show autism-like features, such as social deficits and structural changes in the brain.

However, only a small fraction of children exposed to inflammation in utero are diagnosed with autism.

The findings suggest that a second hit can determine which children exposed to maternal inflammation in utero go on to have autism, says Hong-Ru Chen, a postdoctoral fellow in Alex Kuan’s lab at Emory University in Atlanta, who presented the findings.

Oxygen supply:

The researchers injected pregnant rats with a chemical, polyinosinic-polycytidylic acid, that mimics a viral infection and activates the animals’ immune system.

Pups exposed to inflammation in the womb show several markers of inflammation, including clusters of activated microglia, brain cells that are part of the immune system. They also have elevated levels of inflammatory molecules such as interleukins 6 and 17, both of which are implicated in autism.

When the pups were 10 days old, the researchers exposed some of them to a second challenging condition: They briefly deprived the pups of oxygen, long enough that the brain cells went on alarm but before widespread cell death and extensive brain injury occurred.

Although this condition, called hypoxia-ischemia, is a serious problem in infants, the researchers used only a mild version of it to model a ‘second hit,’ says Kuan, associate professor of pediatrics at Emory University in Atlanta.

A second hit for a baby could be any condition that threatens the health of her brain tissue.

“We don’t know what these potential ‘second hits’ comprise. I think no one knows for sure, but one suspect may be gastrointestinal infection,” Kuan says. A study published in October found that treating pregnant mice with an antibiotic lowers the autism risk associated with maternal infection.

Mice that endured both hits show significantly greater inflammatory activity and cell death than those exposed to only inflammation or only a lack of oxygen.

This finding suggests that exposure to maternal inflammation amplifies the response to oxygen challenge, the researchers say.


  • Sharwan Kumar

    Did the pups show any of the autism like features. If yes what were those specific feaures.

    • Alex Kuan

      We have not compared the behavioral phenotypes of these two conditions, as the focus of study at this moment is neuroimmune responses and brain damage. It will be interesting indeed to see whether the combination of two insults (MIA and mild neonatal injury) cause more severe or additional behavioral deficits. Thanks for your interest and Spectrum to pick up our presentation!

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