Complex Regional Pain Syndrome Medicine

From the Navy to a neuroscience lab: how a daughter’s diagnosis spurred her mother’s career shift

This post originally appeared on StatNews.

Carina Block was working an overnight shift with the U.S. Navy in Japan, preparing oceanographic data for Air Force flight crews, when her husband called. She could sense the fear in Michael’s sobs: Their 4-month-old daughter, Madison, had gone limp as he rolled around with her on their bed. Her eyes had rolled back and her tiny body had begun to convulse. Block dashed home, then drove her husband and daughter to the hospital, trembling as she ran red lights in pounding rain.

“I sort of jumped into action,” she said. “Michael is a very big tough guy, but at heart he’s this big softy. I knew from his voice on the phone that he was crumbling. I knew that between the two of us, I had to show up and be the coherent one to navigate what was about to take place.”

For the next five hours, Madison remained unresponsive. Her parents prepared to say goodbye. Though she recovered, Madison was diagnosed with hydrocephalus, a fluid buildup in deep cavities of the brain. With pressure increasing in her brain, the Navy sent the worried couple to San Diego, where a pediatric neurosurgeon placed a shunt to redirect the fluid.

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Block, then just 23, remained in San Diego with Madison while her husband returned to Japan to pack up and await reassignment from the Marine Corps. At night, after her daughter went to sleep, Block began reading up on the science behind her neurodevelopmental condition.

“It was my first introduction to neuroscience proper,” she said. “I was like, ‘Oh, this explains so much.’” It kindled an interest in completing her college education and studying science.

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Thirteen years after she made the decision to switch careers, Block was lead author of a paper published in Cell Reports this week that found that exposing pregnant mice to diesel exhaust, combined with stressing them out by restricting their nest-building materials, led to abnormal social behavior and lasting changes to the brains of their male pups — though not female offspring. The work points to a potential mechanism through which gestational exposure to pollution and stress can be linked to neurodevelopmental disorders such as autism, which is four times more likely in males than females.

Block is now a postdoctoral researcher at Duke University, a place she never pictured herself ending up. She’d enlisted in the Navy shortly after high school and the military came with a clear path to career advancement. She knew she was good at her job as an aerographer’s mate, and she worried that everyone would be smarter than her if she returned to school. But Madison’s diagnosis changed everything.

“She was there running the ship herself,” Michael said, describing how his wife needed to know why this had happened to their otherwise healthy daughter. The Navy “100% wasn’t what she wanted to do anymore. It was a switch for her; she knew, ‘I’m not gonna settle.’ Her focus and priority was on going back to school.”

After the first few months in a community college classroom, she began to trust that her will would compensate for having to balance school with parenting, as long as she stayed committed – she even lugged calculus books to the hospital when she went into labor with her second daughter.

She finished her bachelor’s degree at the University of California, San Diego, before applying to graduate schools across the country since Michael, who then had a recruiter job in San Diego, didn’t know where he would be sent next. After she decided on Duke, he was able to relocate to North Carolina.

At Duke, she was “highly stressed” and occasionally experienced imposter syndrome, especially when she realized she was the only Latina scientist and the only graduate student with children in her program upon joining. She soon was pregnant with her third daughter, just as her experiments weren’t working and Michael was having to work from 5 a.m. to 11 p.m.

Block remembers a seminar where the presenter said Hispanic women were the least likely demographic to continue in academia, which felt like “in essence saying, ‘least likely to succeed.’” While it wasn’t the intended message of the talk, “it was a message that I internalized,” she said, and she “felt a need to continue forward so that I never had to sit in a room listening to how people like me would be last.”

“I just had to adopt this mentality that there were so many things that were going to be out of my control,” she added. “There was only a small list of things that were actually in my control, so all I could do was just focus on getting that list of things done.”

Block came to Duke with a glowing recommendation – a Navy commanding officer wrote “there’s nothing she cannot do,” and she was equipped with an unparalleled level of maturity and a keen ability to pinpoint what’s actually important. She was accepted psychology and neuroscience professor Staci Bilbo’s lab, which

Block holds Madison, then 4 months old, in their home in Okinawa, Japan. Courtesy Carina Block

studied how exposure to environmental toxins or stress during pregnancy might affect the development of disorders like autism.

It was a topic Block had taken a personal interest in since she began reading neuroscience books in college. Could the jet exhaust she’d been exposed to while in the Navy in Japan have affected Madison’s development, she wondered — especially since her next two daughters did not have any complications. As cases of neurodevelopmental disorders rise globally, Block likes knowing that science might be able to provide answers to such questions.

“I don’t get to control my genetics or the genetics of my husband, but to some extent, I may be able to control environmental factors,” she said. “It’s not some fate written in stone for you. You get to change things. There are definitely things in the environment that we can do to improve the quality of life for our children, ourselves, and for future generations. It’s something that I find really inspiring.”

The Bilbo lab’s current research was motivated by evidence linking early exposure to air pollution with an autism diagnosis among children in Durham County, as well as the observation that some populations are more vulnerable to environmental toxins.

“It’s clearly not just pollution alone but air pollution interacting with other factors,” said Bilbo, a co-corresponding author on the new study. “That’s what was appealing to go after mechanistically.”

The team exposed mice to air pollution and stress and then looked at how their offspring developed. First, the researchers put soot-like diesel exhaust particles in a drop of liquid to deliver to the lungs of pregnant mice. Then, they took away some of the cotton from a teddy bear-like cocoon that the mice use to nest, to mimic the stress of housing instability.

Previously, the team found that exposing pregnant mice to stress or air pollution alone does not affect how their offspring develop. But, together, the two stressors led to an overabundance of connections between neurons – synapses – in male pups in a region of the brain that is important for making sense of social cues. Normally, synapses associated with successful behaviors are maintained and weak synapses are destroyed.

Even though the stressed mothers nursed male and female pups as well as the mothers who were not exposed to stressors, the males were shyer – they liked rubber ducks more than fellow mice – and did not encode social information as well based on brain recordings. The researchers thought the culprit might be a lack of immune cells in the brain called microglia, which normally prune synapses in the brain.

“Microglia can be challenged by inflammatory events in either the in utero environment or postnatally,” Block said. Here, the combined stresses applied to moms shifted the natural diversity of microglia in their male pups so there were fewer synapse-eating microglia.

“The work highlights that environmental toxins and non-chemical stressors during pregnancy can have similar effects on brain development as severe infections,” said Pinar Ayata, a neuroimmunology researcher at the Icahn School of Medicine at Mount Sinai, who was not affiliated with the research.

“For the first time, we see a direct causality between external stressors in the womb, insufficient numbers of synapse-pruning microglia in a specific brain region, an associated abnormality in synapse numbers and brain activity, and shy behavior, similar to what’s seen in neurodevelopmental disorders,” she added.

Bilbo said that while researchers “can’t model something as complex as autism in a mouse,” behavioral changes can be characterized using cognitive deficits. She thinks they could develop models for other neuropsychiatric disorders in the future. Block also said there are limitations with modeling the complexity of housing insecurity in mice, but it is a useful metric since it can be applied chronically.

“We’re trying to model very complex human situations in mice, but we know from recent studies that, for example, neighborhood deprivation is a modifying factor for air pollution and its association to autism,” Block said.

Future research could find a molecular tag to help identify the synapse-pruning microglia so the cells can be tracked to see if they contract, expand, or even convert into other cell types, Ayata suggested. Eventually, the goal could be to develop a therapeutic way to prevent microglia from being manipulated by environmental stressors.

There are limits, though, to what science can do, and Block thinks it is important for environmental changes to come from legislators and regulators. She hopes her lab’s work will spur policies to reduce pollution and ensure healthier pregnancies, especially for working mothers of color.

As for Madison, she’s now 14 and started high school Thursday. Shunts for hydrocephalus can fail or secondary infections can pop up, so Block feels fortunate that she is healthy and the “loudest kid in the house.”

She sings, plays piano, and has an impressive resume of acting gigs in school plays from being Nala in “The Lion King” to Annie. “She is always singing and looking for the next musical adventure,” Block said.

Like her mom, Madison is fascinated by pregnancy and childbirth, but she doesn’t want to be confined to a lab. An aspiring gynecologist, she loves looking at brain scans and talking with doctors at her annual visits.

Correction: This story has been updated to correct the description of Carisa Block’s job in the Navy, the reason that her husband returned to Japan and that he served in the Marine Corps, and the timing of Madison’s diagnosis with hydrocephalus.

This post originally appeared on StatNews.