Mouse study offers clues to brain’s response to concussions

Multiple head hits in succession most worrisome, evidence indicates

soccer players

HEADS UP  The brain needs time to recover between brain injuries, a study in mice suggests. The finding may help doctors understand potential injuries to athletes, including soccer players who repeatedly head the ball.

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The brain can bounce back after a single head hit, but multiple hits in quick succession don’t give the brain time to recover, a new study suggests. Although the finding comes from mice, it may help scientists better understand the damage caused by repetitive impacts such as those sustained in football, soccer and other contact sports.

The results, published in the March issue of the American Journal of Pathology, hint that a single, mild head hit isn’t necessarily cause for alarm. “There are things to be afraid of after a concussion,” says study coauthor Mark Burns of Georgetown University Medical Center in Washington, D.C. “But not every concussion is going to cause long-term damage.”

Burns and his colleagues subjected some mice to a single, mild head hit. The relatively weak hit consistently slowed anesthetized mice’s return to consciousness, but didn’t cause major trauma. The impact was designed to mimic a mild traumatic brain injury, or concussion, in a person.

Tests a day after the impact showed that about 13 percent of dendritic spines, docking sites that help connect brain cells, had vanished in a particular part of the brain. Three days after the injury, these missing connections reappeared, even surpassing the original number of connections.

This fluctuating number of dendritic spines may actually help the brain recover, Burns says. “The cells weren’t dying,” he says. “They were responding to the injury.”

The team expected to see even more dendritic spines vanish with recurring hits. But that’s not what happened. Mice subjected to 30 mild hits over six weeks didn’t show a dip in connections followed by a resurgence, the team found. When the hits kept coming, the dendritic spine count stopped fluctuating. “This rebalancing doesn’t happen,” Burns says.

When mice were given a week off between injuries, their brains once again showed signs of brain cell connection loss and recovery, suggesting that time between injuries resets the brain in a way that lets it handle another hit.  

Pediatrician Danny Thomas of Children’s Hospital of Wisconsin in Milwaukee says that the results highlight the dangers of reinjury. “As a clinician, this says when people have a concussion, they shouldn’t expose themselves to another head injury,” he says. “That’s the worst thing they can do.”

Brain damage from mild hits in quick succession lingered. A year after the injuries, the researchers found inflammation in the mouse brains’ white matter, which carries signals from one brain area to another. What’s more, these animals had trouble balancing on a rotating rod and showed signs of anxiety.

Though preliminary, the results “add another small piece to the ever-growing puzzle of what’s happening after repetitive traumatic brain injury,” says neuroscientist Ramesh Raghupathi of Drexel University College of Medicine in Philadelphia.

Yet Raghupathi cautions that it’s hard to design experiments that yield meaningful information for people, particularly those at risk of recurring concussions. “As you can imagine, those of us who do animal work could spend a lifetime designing experiments that vary the number of hits, the interval between hits, and the intensity of each hit,” he says. 

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