Childhood concussions may trigger long-term brain changes

A new study in mice reports that concussions sustained early in life can cause subtle brain changes that re-emerge later in life. The findings, published in Experimental Neurology, may have significant implications for understanding the long-term impact of head injuries in children.

Led by Andre Obenaus, a professor of biomedical sciences at UC Riverside's School of Medicine, the study used advanced brain imaging techniques to identify initial signs of injury that appeared to resolve, only to return months later as more severe white matter damage.

Obenaus explained that a single concussion in early life can lead to lasting changes in white matter - the fibers in your brain that serve as communication pathways - potentially altering brain structure and function throughout an individual's lifetime. The findings highlight the need for ongoing monitoring and care following head injuries in children, he said.

"We've known that white matter is vulnerable after traumatic brain injury," Obenaus said. "What's been missing, however, is a comprehensive, long-term look at how a single juvenile concussion affects the brain over time. Our findings fill that gap and show that brain changes from early-life concussions may not be immediately obvious, but they can reappear and worsen over time."

In their experiments, Obenaus and his colleagues gave adolescent mice a concussion and then conducted MRI scans at seven different points over 18 months - the majority of the animal's lifespan. The team used a specialized type of imaging known as diffusion tensor imaging, which maps white matter and helps detect microstructural damage.

They found that the injury disrupted the normal growth and organization of the corpus callosum, a vital white matter tract that connects the left and right sides of the brain. These changes were exacerbated by 18 months after injury. The researchers observed early disruptions in a key white matter metric called fractional anisotropy, a measure of the asymmetry as water moves through the brain. While these changes appeared to normalize shortly after the injury, significant deterioration reappeared later in life, particularly following more severe concussions.

In uninjured mice, the researchers found white matter structure showed steady, healthy development over time. But in mice that experienced concussion, they saw an early plateau in in white matter diffusion characteristics. Particularly in the more severe injury group, they found changes in brain imaging measures with age, pointing to long-term disruption in brain connectivity.

"These effects were most pronounced in the frontal portion of the corpus callosum that is involved in many key cognitive functions," Obenaus said.

At the end of the study, the researchers examined the brains for signs of inflammation. They found notable changes in microglia, the brain's immune cells, and, to a lesser extent, astrocytes, which help to maintain brain function. Their statistical analysis linked microglial activation to the long-term white matter changes, suggesting neuroinflammation may play a key role in delayed brain damage.

"We found the shape and behavior of microglia and astrocytes were significantly altered in concussed mice, suggesting the concussion set off a cascade of biological changes that persisted long after the initial injury," Obenaus said. "This shows a single concussion during childhood doesn't just cause temporary symptoms. It can trigger subtle but lasting changes to the brain's structure."

Although the study was conducted in mice, the findings approximate patterns seen in humans. Children and adolescents who suffer a concussion often recover quickly, but research has increasingly shown that brain connectivity and cognitive function can deteriorate years later.

"Our work reinforces the importance of long-term monitoring," Obenaus said. "Children who experience a concussion should not be declared 'fully recovered' based only on short-term symptoms. Subtle changes may take years to show up and, by then, interventions may be more difficult."

Obernaus was joined in the research by Brenda P. Noarbe, Sean D. Noarbe, and Yu Chiao Lee of UC Irvine; Jeong Bin Lee of Loma Linda University; and Polina E. Panchenko, Fang Tong, Claire Bottini, and Jerome Badaut of the French National Centre for Scientific Research.

The research was supported by grants from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.

The title of the paper is "Progressive lifespan modifications in the corpus callosum following a single concussion in juvenile male mice monitored by diffusion MRI."

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