Enriched environment improves wound healing in rats

Improving the environment in which rats are reared can significantly strengthen the physiological process of wound healing, according to a report in the open-access journal PLoS ONE.

Researchers from the Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital (MGH) and Shriners Burns Hospital found that giving rats living in isolation the opportunity to build nests led to faster and more complete healing of burn injuries than was seen in isolation-reared rats without nest-building materials. The study also found evidence that this effect was associated with altered gene expression in stress-associated structures in the brain.

“These findings are consistent with other animal studies that show how stress and social deprivation reduce physical well being, but our study is novel in showing that the detrimental effects on physical health can be reversed by environmental stimulation” says John B. Levine, MD, PhD, of the MGH Department of Psychiatry, senior author of the paper.

Previous research indicated that a more stimulating environment improves maternal behavior in rats – probably through the effects of oxytocin, a hormone involved with maternal attachment and bonding – and that stress reduces wound healing in both animals and humans. An earlier study by members of the MGH/Shriners research team found that rats raised in isolation had both poor wound healing and changes in the activity of stress-associated brain structures. The current study was designed to examine whether environmental enrichment can reduce the impact of stress on wound healing and to investigate associated changes in brain activity and behavior.

Young rats that had just been weaned were placed either in cages shared with other rats or into isolation cages. Along with standard bedding materials, some of the isolated animals also received small squares of cotton called Nestlets that they would tear up and arrange into nests. The nesting materials were replaced twice a week, and each time the rats built themselves new nests. An experiment designed to test wound healing found significant difference among these groups. Four weeks after a burn injury was administered under anesthesia, 92 percent of the group-reared rats had healed well, compared with only 12 percent of the isolation-reared rats without nesting materials. But among the isolation-reared rats given nesting materials, 64 percent were determined to have healed well.

Another experiment showed that a daily dose of oxytocin had the same effect on wound healing as did access to nest-building materials. A third experiment showed that the opportunity to build nests reduced the hyperactive behavior typically seen in isolation-reared rats and also had effects in the hippocampus – a brain structure known to be key to the stress network – increasing the expression of genes previously shown to be underexpressed in isolation-reared animals.

“The fact that giving these animals a behavioral intervention changed not only their behavior but also their physical health raises important mind-body questions that require further investigation in humans as well as animal models,” says Gregory Fricchione, MD, director of the Benson-Henry Institute and co-corresponding author of the PLoS ONE report. “It sets the stage for further studies to identify the mechanism accounting for this phenomenon.”

Herbert Benson, MD, the founder and director emeritus of the Benson-Henry Institute and a co-author of the PLoS ONE report adds, “We know that the behavioral techniques we have been using to help patients for decades can improve health in several ways, and this study is adding to our understanding of exactly how that happens. Learning more about the mechanisms underlying these effects can only add to our ability to help patients cope with a wide array of health challenges.”

Levine is an assistant clinical professor of Psychiatry and Fricchione is a professor of Psychiatry at Harvard Medical School. Levine is also director of Child and Adolescent Psychiatry at Saint Francis Hospital in Hartford, Conn. Additional co-authors of the PLOS One study are Antonia Vitalo, Jonathan Fricchione, Monica Casali, Yevgeny Berdichevsky, Francois Berthiaume, and Martin Yarmush of the MGH Center for Engineering in Medicine and Shriners Burns Hospital; Elizabeth Hoge, MGH Psychiatry; and Scott Rauch, McLean Hospital. The study received funding from the John Henry Foundation, the Benson-Henry Institute for Mind Body Medicine at Massachusetts General Hospital, and the Medical Research Programs of the Shriners Burns Hospital – Boston.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.