Researchers say it’s important to avoid a second concussion before the first one heals, because repeated concussions multiply the damage. Cognitive rehabilitation exercises, like specially designed video games, may also help boost brain reserve.

Follow-up care to treat symptoms such as headaches, dizziness, depression and anxiety can help prevent lasting disability, according to Manley, professor of neurosurgery. Manley is the principal investigator of the multicenter TRACK-TBI (Transforming Research Clinical Knowledge in Traumatic Brain Injury) study, the largest precision medicine study of TBI to date, which is tracking thousands of people nationwide who visit the emergency room for head trauma.

TRACK-TBI has found that less than half of patients who visit the emergency room for concussion received any follow-up within three months, including educational materials and doctor’s visits.      

“Many of those who aren’t being seen are suffering and need medical attention,” he said. “It’s a major gap in care that represents an important public health issue in this country.”

In the coming years, TRACK-TBI will attempt to answer some crucial questions, such as the value of blood-based biomarkers and advanced MRI imaging techniques in diagnosis and the role of genetics. It will also test new phase II drugs in clinical trials.

In Mice, Clues to a Cure

There are glimmers of hope that the harm from concussions can be reversed.

In mice that have sustained concussions, treatment with a molecule called ISRIB (which stands for Integrated Stress Response InhiBitor) was able to fully reverse cognitive damage. Even more surprising, the treatment was effective when given months after the injury, which could potentially translate to years after injury in humans, and the reversals appear to be permanent. These studies were also supported by a Weill Innovation Award.

“We were blown away,” said Susanna Rosi, PhD, who co-led the ISRIB study with the discoverer of the molecule, Peter Walter, PhD. Her team repeated the experiment three times and also tested different animal models of concussion, just to make sure, and saw the same results.

“Despite what trauma does to the brain, it seems there are reserves, at least in the rodent brain, that we can use to make the brain function again,” said Rosi, who directs neurocognitive research at the Brain and Spinal Injury Center. The stunning results in mice offer hope for reversing the effects of TBI in humans.

ISRIB works by resetting a normal biological reaction that can go awry in brain injury.

Under stress, cells activate a stress response, which shuts down the cells’ production of proteins as a temporary protective mechanism. A traumatic brain injury can activate the stress response chronically in brain cells, impairing the brain’s ability to form new memories. ISRIB removes the block and appears to restore normal brain function.

It’s still unclear how the cellular stress response is involved in neurodegenerative disease, though it’s known to increase with normal aging, says Rosi.

Despite the unanswered questions, like if the ISRIB treatment effects will translate to humans, researchers say they are generally optimistic about the future of concussion treatment.

“People don’t understand what a new field this is,” said Yaffe. Her research is among those that have brought public awareness to the dangers of concussions in just the last few years.

“We have to be extremely positive that we have so many tools and resources we didn’t have five years ago,” said Rosi, naming high-resolution imaging, single-cell sequencing, and more precise biomarkers as important advances.

And a silver lining: concussion research may yield insights into ways to fight Parkinson’s and dementia. “Unlike any other risk factor we know for neurodegenerative disease, TBI has a specific time stamp,” said Gardner. “It may be a unique opportunity to intervene at the earliest possible stage.