Scientists find out the cause of bowel disease in premature children

Photo Source: David Hackam
In a report published December 12 in the journal Science-Translational Medicine, U.S. scientists say they have discovered the molecular cause of necrotical disease in mice using necrotical colitis (NEC), a potentially fatal disease that causes intestinal necrosis in premature babies. Based on this finding, researchers will be able to work with scientists studying brain inflammation to identify potential drugs that can reverse brain damage in mice.
David Hackam is director of pediatric surgery at Johns Hopkins University and professor of surgery, pediatrics and molecular biology. "There was no clear understanding of what causes NEC, and the only solution for serious cases is to surgically remove the infant's necrotated intestine," he said. But surviving NEC patients still have sequelae, including severe cognitive impairment. This problem has only recently made a breakthrough. Although
exact cause of NEC in newborns is not yet known, scientists already know that the disease occurs in premature babies who are stressed by feeding formula and suffering from bacterial infections. So the team developed a NEC mouse model that separated newborn mice from the mother mice and fed them formula, placing them in a hypoxia chamber twice a day as a stressor for four days. At the same time, to make sure the mice carried the same germs as the children, the researchers fed them feces from babies with severe NEC. According to Hackam, not only do these mice develop NEC, but their brains suffer the same damage as humans, and brain function is impaired in old age. Currently, they are looking into the causes of NEC-related brain damage in these mice.
study, they first looked at whether immune cells in the brains of these NEC mice, known as small glial cells, were activated, which means some inflammation. As a result, small glial cells are indeed activated. Other studies have shown that a protein called TLR4, when combined with bacteria in the gut, can also activate small glial cells in the brain. The researchers genetically engineered mice to make small glial cells free of TLR4, and then let the mice develop NEC. The results showed that none of the mice had NEC-related brain injury, suggesting that TLR4 was the cause of the injury.
, the team hopes to understand what substances in the intestinal disease can cause brain damage. Their previous studies have shown that TLR4 proteins are also present in the intestines. Hackam says high levels of TLR4 occur in the intestines during embryonic development, but decline after the baby's full moon is born. In contrast, TLR4 in the intestines of premature children remains at a high level.
TLR4 in the intestines of children with NEC causes cells to release another protein, HMGB1. The team genetically engineered mice to lack HMGB1 and then gave them NEC. These mice had fewer small glial cells in their brains than mice with NEC and were not genetically engineered, meaning that HMGB1 from TLR4 in the inflamed intestine was indeed the cause of NEC-related brain damage.
one of the greatest strengths of our school is that it has outstanding scholars in different fields, " says Jackam, a school official. I came here in 2014 and Sujatha Kannan was one of the first colleagues I met. He was studying the rabbit's brain damage. Their latest results suggest that an anti-cancer treatment to prevent cerebral palsy can be performed on the rabbit brain. "So the two decided to work together to see if this approach would work for mice with NEC.
researchers fed mice with NEC nanoparticles containing antioxidants and used fluorescent molecular markers to examine the brains of mice to see where luminescent molecules had accumulated. Eventually they did find that the glowing areas of the brain were where small glial cells were active. In addition, the mice had fewer active glial cells in their brains, suggesting that nanoparticle drugs could protect the brain from NEC-related brain damage.
Really need to change the way we think about NEC as an intestinal disease, but as an intestinal-brain disease," says Hackam, a government executive. Hackam added: "While the disease is immediately reflected in the intestines, neonologists should also focus on brain protection treatments, including faster surgery, intestinal rest and antibiotic use."
is a devastating disease, but now we know its underlying more clearly at the molecular level, " says Mr Hackam. We are eager to see if it works for other models and patients so that it is eventually possible to better help these babies and their parents. (Source: Zhao Xixi, China Science Daily)