UTI After Brain Injury Worsens Cognitive Decline, Study Shows

A urinary tract infection arriving in the weeks after a moderate brain injury can amplify the cognitive damage the injury itself causes. That's what researchers at Ohio State University discovered in a recent study using mice, published in the Journal of Neurotrauma—the first time anyone has examined how a bladder infection compounds the neuroimmune and cognitive fallout of traumatic brain injury.

The finding matters because UTIs are far more common in brain injury survivors than most clinicians seem to appreciate. About 15 percent of adults who have experienced a traumatic brain injury develop a urinary tract infection within the first year. Those infections are responsible for up to one-fifth of all hospital readmissions in that same window. Yet the cognitive consequences of a UTI layered on top of a TBI have largely gone unexamined—until now. Olga Kokiko-Cochran, an investigator in the Chronic Brain Injury Program at Ohio State and an associate professor of neuroscience, led the work. "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," she said. "We thought UTI could be something that's having a much bigger impact on recovery after brain injury than we currently appreciate."

The researchers worked with four groups of female mice. Two groups received a moderate brain injury—the kind that might result from a fall, the leading cause of traumatic brain injury in humans. Two control groups underwent surgery but received no brain injury. Three days after the initial procedure, the team introduced uropathogenic E. coli bacteria, the primary culprit behind most UTIs, into the urethras of half the mice in each group. The other half received a control treatment. Six days after the injury, behavioral testing revealed the pattern: the brain injury alone impaired spatial memory in the mice. But when a UTI followed the injury, the cognitive damage became dramatically worse. "UTI following the injury greatly exaggerated those cognitive impairments," said Zachary Zimomra, the study's first author and a neuroscience research associate in Kokiko-Cochran's lab.

The mechanism appears to involve the brain's immune response. The researchers found that the combination of brain injury and bladder infection triggered delayed increases in two inflammation-related proteins across multiple regions of the injured brain. This suggested that brain immune cells were reacting not just to the initial trauma but to the infection as well. Intriguingly, the team also observed changes in bladder immune cells following brain injury alone—a clue that something about the injury itself may make the bladder more vulnerable to infection. "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."

When the researchers examined inflammatory signaling in more detail, they found that a cytokine called IL-6 was elevated in the blood after brain injury, then suppressed by the UTI—suggesting that clearing the infection triggered an anti-inflammatory response. The cellular changes observed in both the bladder and brain hint at a biological conversation between the two organs that goes beyond their known neural connection related to urination. Understanding that dialogue could eventually lead to strategies for preventing infections after brain injury, which in turn could improve long-term recovery. "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," Zimomra said. "It may be something with the bladder itself."

The initial study focused on female mice because women are 30 times more likely than men to develop a UTI—a disparity that holds true in the general population, where bladder infections affect roughly 400 million people annually. But brain injury followed by UTI is not a problem limited to women. Kokiko-Cochran said future research will include both male and female animals, and the team plans to dig deeper into how the brain and bladder communicate and why that communication appears to amplify cognitive decline when both organs are compromised. The work was supported by pilot funding from Ohio State's Chronic Brain Injury Program and Institute of Brain, Behavior, and Immunology. For now, the message is simple: a UTI after a brain injury is not something to overlook. "Sometimes these common experiences that are overlooked are important," Kokiko-Cochran said, "and I think we can't presume that an infection of any sort is no big deal."