WASHINGTON, Feb. 19, 2020 /PRNewswire/ -- An enriched environment—with increased opportunities for physical activity, socialization and exploring novel stimuli—helped lessen functional, anatomical and cellular deficits in an experimental model of brain damage caused by oxygen deprivation at birth. What's more, recovery of the brain's white matter required a combination of all experimental interventions, not just a single intervention, suggests a new study led by researchers at Children's National Hospital. Their findings, published online Feb. 19, 2020, in "Nature Communications," could lead to new treatments for children affected by this condition.
About 450,000 babies are born preterm in U.S. every year, a number that continues to rise, says senior author Vittorio Gallo, Ph.D., chief research officer for Children's National Hospital and scientific director for Children's National Research Institute. Oxygen deprivation caused by immature lungs or birth injuries is a common consequence of prematurity, which leads to permanent neurological deficits and disabilities, Gallo explains.
Premature babies require minimal handling for their first months of life in order to eliminate stressful stimuli and optimize their development. Efforts have been made to switch from the noisy and crowded environment of the older neonatal intensive care units to new, quiet private family rooms in order to eliminate noise and light. However, recent studies suggest that infants that were treated in private family rooms had lower language and motor scores compared to the infants in open wards, raising questions about the ideal level of stimulation that premature neonates require in order to achieve optimal brain development. The mechanisms by which environmental stimuli positively affect brain development in the early neonatal period and better neurological outcomes remain unclear.
To determine how enriched environments may affect recovery for newborns who suffer brain injury after birth, Gallo and colleagues leveraged a preclinical model of newborns exposed to low oxygen levels shortly after birth. These experimental models had brain damage similar to premature human babies with hypoxic brain injuries.
After injury, some of these experimental models grew up in standard enclosures, with little more than nesting materials, a few other cage mates, and access to food and water. Others grew up in enriched environments: larger enclosures equipped with a running wheel as well as objects of differing sizes and colors that were switched out frequently, and more cage mates for enhanced socialization.
When these preclinical models were young adults, the researchers assessed how well they performed on a functional test of motor skills in which both groups scurried up a narrow, inclined beam. While foot slips were common in both groups, those raised in an enriched environment had about half as many as those raised in the less-stimulating enclosures.
When researchers examined the brains, they found that these functional improvements were linked to significantly enhanced division and maturation of oligodendrocytes, cells in the brain's white matter that support nerve cells and produce myelin, a fatty insulating sheath that covers the long extensions that connect nerve cells to each other and to other parts of the body. Indeed, consistent with the cellular and functional findings, the white matter of experimental models raised in enriched environments had significantly more myelin content than that of counterparts raised in the simpler environment.
Further experiments showed that for these improvements in function and anatomy to occur in experimental models raised in the enriched environments, they needed all three elements: enhanced physical activity, socialization and cognitive stimulation from novel objects. Additionally, exposure to these elements needed to start early and be continuous and long term. Those experimental models that weren't raised in a completely enriched environment or whose exposure to the environment started later, was interrupted, or was cut short didn't have any improvements in function and white matter recovery.
Digging deeper, Gallo and colleagues employed next generation sequencing to investigate oligodendrocyte gene expression in these animals, identifying broad differences in networks of genes involved in oligodendrocyte development between the two groups.
Gallo notes that these results and future studies to better understand the effects of enriched environments could lead to better ways to care for premature babies that help lessen or prevent the long-term consequences of oxygen deprivation.
In addition to Gallo, other Children's National co-authors include Thomas A. Forbes, Ph.D., co-lead author, Evan Z. Goldstein, Ph.D., and co-authors Beata Jablonska, Ph.D., Joseph Scafidi, D.O., Katrina L. Adams, Ph.D. and Kazue Hashimoto-Torii, Ph.D.; additional authors include Jeffrey L. Dupree, Ph.D., Virginia Commonwealth University; and Yuka Imamura, Ph.D., Penn State University.
Financial support for research described in this post was provided by the District of Columbia Intellectual and Developmental Disabilities Research Center (DC-IDDRC) under award No. U54HD090257, the National Institutes of Health (NIH) under award Nos. R37NS109478, F31NS100277, F32NS106723 and 5R01NS099461. Microscopic analyses were carried out at the Children's National Research Institute Cell and Tissue Microscopy Core, which is supported by DC-IDDRC. The study authors also acknowledge the support of the CRI Bioinformatics Unit, a partnership between the Children's Research Institute, the Center for Genetic Medicine Research, the Clinical Translational Science Institute at Children's National (CTSI-CN) and the DC-IDDRC. The CTSI-CN is supported by the NIH under grant Nos. UL1TR001876 and KL2TR001877.
Summary: Preclinical model of oxygen deprivation, a common consequence of prematurity, showed better recovery when exposed to a combination of increased physical activity, socialization and cognitive stimulation
About Children's National Hospital
Children's National Hospital, based in Washington, D.C., celebrates 150 years of pediatric care, research and commitment to community. Volunteers opened the hospital in 1870 with 12 beds to care for Civil War orphans. Today, 150 years stronger, it is the nation's No. 6 children's hospital. It is ranked No. 1 for newborn care for the third straight year and ranked in all specialties evaluated by "U.S. News & World Report." Children's National is transforming pediatric medicine for all children. In 2020, it will open the Children's National Research & Innovation Campus, the first in the nation dedicated to pediatric research. It has been designated twice as a Magnet® hospital, demonstrating the highest standards of nursing and patient care delivery. This pediatric academic health system offers expert care through a convenient, community-based primary care network and specialty outpatient centers in the D.C., metropolitan area, including the Maryland and Northern Virginia suburbs. Children's National is home to the Children's National Research Institute and Sheikh Zayed Institute for Pediatric Surgical Innovation and is the nation's seventh-highest NIH-funded children's hospital. It is recognized for its expertise and innovation in pediatric care and as a strong voice for children through advocacy at the local, regional and national levels.
SOURCE Children’s National Hospital