Bladder infection after brain injury worsens cognitive problems

An error occurred while preparing your download

Bladder infection after brain injury worsens cognitive problems

Animal study also shows post-injury UTI alters brain immune cells

A urinary tract infection that follows a moderate brain injury can worsen cognitive problems caused by the injury, new research in mice shows.

People who have experienced a traumatic brain injury (TBI) are susceptible to many types of infections, especially in the lungs. Yet previous studies have shown that bladder infections in this population are not uncommon: 15% of adult brain injury patients experience a urinary tract infection (UTI) within a year, and UTIs are responsible for up to 20% of hospital readmissions that occur within a year after a TBI. In addition, UTIs are known to cause delirium-like symptoms in medically vulnerable people.

This new study, led by researchers at The Ohio State University and published recently in the Journal of Neurotrauma, is the first publication to examine neuroimmune and cognitive effects of a post-brain injury bladder infection in an animal model.

"This very common infection is happening in TBI survivors and probably those who don't even report it and go to the hospital, and it's associated with observed and perceived cognitive changes. We thought UTI could be something that's having a much bigger impact on recovery after brain injury than we currently appreciate," said senior author Olga Kokiko-Cochran, an investigator in the Chronic Brain Injury Program and the Institute of Brain, Behavior, and Immunology (IBBI) at Ohio State and associate professor of neuroscience in the College of Medicine.

"Let's not overlook UTI," she said. "Sometimes these common experiences that are overlooked are important, and I think we can't presume that an infection of any sort is no big deal."

Injuries in this work are moderate in severity and resemble the type of TBI that could result from a fall - the most common cause of traumatic brain injury.

The experiments involved four groups of female mice: those with a TBI (performed surgically under anesthesia) and "sham" mice, which had surgery but no brain injury. Three days later (again, under anesthesia), either uropathogenic E. coli bacteria, the main cause of UTIs, or a control treatment was injected into their urethras.

Results from behavioral tests six days after injury showed that the TBI impaired the animals' spatial memory, and UTI following the injury "greatly exaggerated those cognitive impairments," said first author Zachary Zimomra, a neuroscience research associate and manager of Kokiko-Cochran's lab.

That UTI-induced cognitive impairment was associated with delayed increases of two inflammation-related proteins in two different cell types in several regions of the injured brains compared to controls. This finding suggested that brain immune cells were responding to not just the TBI, but to the bladder infection as well. And bladder immune cells changed after brain injury alone - an intriguing clue that could help explain why infections follow a TBI.

"Maybe there's some susceptibility we don't even appreciate," Kokiko-Cochran said. "Because we do see, post-TBI, a higher immune cell presence in the bladder."

The team looked further into changes in inflammatory protein signaling linked to the injury and infection, finding one cytokine, IL-6, elevated in the blood after TBI and then muted by the UTI - suggesting that clearance of the infection prompted anti-inflammatory activity.

Cellular changes seen in the bladder and brain also offer hints at the biology behind post-injury infection that researchers plan to investigate further. A better understanding of how the brain and bladder communicate - beyond their known neural connection related to urination - could lead to infection prevention strategies that improve long-term TBI outcomes, the researchers say.

"Clinically, there is something about UTI that causes a behavioral change in cognition that you don't necessarily see from influenza or a cold or some other infection. It may be something with the bladder itself," Zimomra said. "We want to learn what happens within the brain, but also how bladder change following TBI exaggerates or enhances these behavioral effects."

UTIs affect 400 million people worldwide each year, and females are 30 times more likely than males to experience a bladder infection - which is why this initial study was done in female mice. But UTI after a brain injury is not restricted to females, meaning future research will include animals of both sexes, Kokiko-Cochran said.

"This has been an opportunity for our lab to contribute something new that has, we think, important translational relevance and could raise awareness and help us think about how this type of infection was layered on top of a brain injury," she said. "There's a lot more we can do to understand the brain-bladder connection."

This work was supported by pilot funding from the Chronic Brain Injury Program and IBBI at Ohio State. Co-authors included Christina Lepak, Rebecca Boland, Morgan Taylor, Amber McCraw, Irene Crescenze and Dana McTigue of Ohio State, and Henry Schreiber of Washington University School of Medicine.

More Ohio State News