Elizabeth J. Kovacs, PhD, Receives Supplement to NIH Grant on Aging and Burn Trauma

Why do older burn patients often suffer mental decline after their injury, while younger burn patients don’t show as dramatic cognitive effects? It’s a question Elizabeth J. Kovacs, PhD, vice chair of research at the University of Colorado Department of Surgery, has been exploring for years. Kovacs has recently expanded her research on aging and injury to include cognitive function. An administrative supplement to her ongoing National Institutes of Health R01 grant on the topic will fund further investigation of the issue and its causes, including the excessive inflammation burn injuries can cause in multiple organ systems.

“This includes leakiness of the protective barriers of the gut and the brain, leading to aberrant cognitive function including delirium and dementia,” Kovacs says. “In the burn population, patients experience delirium dementia because of their injuries and the environment they're in, such as an intensive care unit. We're trying to figure out what we can do early on to monitor their care and to be able to fix that. This grant will expand our research into neuroinflammation and cognitive function.”

Investigating ‘inflammaging'

Kovacs says that clinical and experimental evidence show that aging causes an elevated basal inflammatory state, referred to as “inflammaging,” that can contribute to deficits in tissue injury and repair. 

“We believe that inflammaging is caused, in part, by translocation of bacterial products from the intestines, and that exposure to these products triggers the production of pro-inflammatory proteins,” she says. “Neuroinflammation and burn injury in the aged population are correlated with breaches in the blood brain barrier, delirium, and other signs of cognitive decline. We hypothesize that age-related increased gut leakiness and altered intestinal microbiome after burn injury leads to heightened systemic inflammation and breach of the blood brain barrier, neuronal damage, and cognitive decline.” 

Role of the gut

Using animal models of burn-associated inflammation, Kovacs and the researchers in her lab are studying age-related differences in cognition levels and emotional stability. Building off work by other researchers establishing the importance of the gut microbiome on progressive neurologic disorders such as Alzheimer's disease, Kovacs’ team is investigating age-related mechanisms responsible for early damage to the gut and blood brain barriers after burn injury in hopes of identifying novel strategies to reduce the impact of post-injury neuroinflammation and mental decline.

“We know that the microbiome in the gut is dramatically altered in aging and burn injury, and we're investigating how to restore a more youthful microbiome in older subjects and reduce the leakiness of the gut with drugs that are commercially available for other purposes,” she says. “These studies will expand our understanding of how advanced age alters the gut in the context of burn injury and the impact of intestinal permeability on neuroinflammation, a hallmark of Alzheimer’s disease and related disorders. It is our hope that this work will lead to the development of novel therapies to treat the excessive inflammatory response and cognitive dysfunction seen in older patients suffering from traumatic injuries and a variety of other disorders.”