Through research fueled by fines on speeding tickets and traffic violations, Rutgers University scientists have discovered how lithium — a powerful drug long used to treat bipolar disorder — can also help preserve brain function in patients who suffer traumatic brain injury.
The findings, published Monday in the Scientific Reports section of the international journal Nature, are particularly important because most medications now used to treat brain injury focus on the symptoms and pain relief, not preventing further damage. Traumatic brain injury, or TBI, is a major cause of death and disability, impacting some 1.7 million people each year, including more than 12,000 in New Jersey.
A new use for lithium
Researchers discovered that the mood stabilizer lithium, approved decades ago to treat bipolar disorder and serious depression, also protected healthy brain cells from a toxic buildup of chemicals that often result from a violent blow to the head. An analog of the drug rapamycin, an immunosuppressant also used to treat pancreatic cancer, had similar effects, the scientists found.
The work, led by Bonnie Firestein, a professor in Rutgers Department of Cell Biology and Neuroscience, was funded by a three-year grant from the New Jersey Commission on Brain Injury Research. Founded in 2004, the commission has provided tens of millions of dollars in grants to support work underway in the Garden State with money raised through a $1 fee on traffic tickets for moving violations like speeding, cellphone use while driving, and related offenses.
“The public doesn’t often understand what we do with the money,” Firestein said, adding that she felt lucky to work in a state that supports such robust scientific research. “It’s important for people to realize that their speeding tickets are going to this fund.”
TBI is caused by a blow to the head that disrupts normal brain function; it can result in memory loss or other cognitive impairment, physical disabilities including vision and hearing loss, or emotional consequences such as depression and personality change. The condition is not caused by heredity or aging, but can result from other incidents like strokes, brain tumors, or drug overdoses. According to the federal Centers for Disease Control and Prevention, TBI kills 153 people every day nationwide, or more than 50,000 a year.
Common concussions
“The most common traumatic brain injury that people deal with every day is concussion which affects thousands of children each year,” Firestein said. These can be particularly hard to diagnose, she said, since children may not be as open about their symptoms.
To help protect against long-term brain damage, New Jersey lawmakers have spent several years working on a plan that would require children who suffer a concussion at school to be cleared by a healthcare professional before they can return to class. The latest version passed the Assembly in September but awaits a final vote in the Senate.
Firestein said she and her colleagues will start work this summer on research to pinpoint biological markers that are tied to traumatic brain injury to make the condition easier to diagnose, especially in children. But it is also important to find drugs that prevent long-term damage, she noted, a goal that is the focus of a number of New Jersey-based research projects.
“The hope is to combine a lot of these strategies,” Firestein said. Other researchers are examining the role of immune-system responses and ways to strengthen healthy cells, she added.
Most recent work
The focus of her most recent work, conducted with help from experts at the University of Pennsylvania, was to reduce the impact of the chemical glutamate. Under normal situations, the substance assists with learning and memory. But a head injury can trigger a massive release of glutamate and the buildup becomes toxic, causing damage or death in the healthy cells surrounding the wound, she explained.
“The problem [with TBI] is, a number of cells start to die and some are kind of hanging in the balance, hanging on a cliff,” Firestein explained. “And you want to keep those hanging on a cliff from dying.”
The Rutgers scientists discovered that lithium and a form of rapamycin — both already approved by the Federal Drug Administration for other uses — could be directly applied to help protect these healthy cells. These drugs blocked the glutamate from sending signals to the healthy cells that would otherwise trigger their demise.
“We worked directly on trying to keep these nerve cells functioning,” Firestein said. “The question was, how do we reduce the toxic signals in the brain so the neurons survive.”
Firestein said their research allowed scientists to “sort out” how these two drugs work to block the glutamate messages traveling from damaged to healthy cells. But further research remains to determine how these medicines could work in animals and humans, so it may take some time before the treatment is available for patients.
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