December 9, 2009
CONTACT: Kim Guenther
With Amino Acid Diet, Improvement After Brain Injury
Animal Study May Set Stage for Treating Brain Damage in People
PHILADELPHIA – Neurology researchers have shown that feeding amino acids to brain-injured animals restores their cognitive abilities and may set the stage for the first effective treatment for cognitive impairments suffered by people with traumatic brain injuries.
“We have shown in an animal model that dietary intervention can restore a proper balance of neurochemicals in the injured part of the brain, and simultaneously improves cognitive performance,” said study leader Akiva S. Cohen, PhD, a neuroscientist at the University of Pennsylvania School of Medicine and The Children’s Hospital of Philadelphia.
The study appears online in the Proceedings of the National Academy of Sciences.
If these results in mice can be translated to human medicine, there would be a broad clinical benefit. Every 23 seconds, a man, woman or child in the United States suffers a traumatic brain injury (TBI). The primary cause of death and disability in children and young adults, TBI also accounts for permanent disabilities in more than 5 million Americans. The majority of those cases are from motor vehicle injuries, along with a rising incidence of battlefield casualties.
Although physicians can relieve the dangerous swelling that occurs after a TBI, there are currently no treatments for the underlying brain damage that brings in its wake cognitive losses in memory, learning and other functions.
The animals in the current study received a cocktail of three branched chain amino acids (BCAAs), specifically leucine, isoleucine and valine, in their drinking water. Previous researchers had shown that people with severe brain injuries showed mild functional improvements after receiving BCAAs through an intravenous line.
BCAAs are crucial precursors of two neurotransmitters—glutamate and gamma-aminobutyric acid, or GABA, which function together to maintain an appropriate balance of brain activity. Glutamate excites neurons, stimulating them to fire, while GABA inhibits the firing. Too much excitement or, too little, and the brain doesn’t work properly. A TBI upsets the balance.
In particular, a TBI frequently damages the hippocampus, a structure deep in the brain involved in higher learning and memory. In the current study, the researchers found that an injury to the hippocampus reduced levels of BCAAs. Although overall levels of glutamate and GABA were unchanged, the loss of BCAAs disturbed the critical balance of neurotransmitters in the hippocampus, making some localized regions more excitable and others less excitable. Cohen’s team tested the hypothesis that providing dietary BCAAs would restore the balance in neural response.
In this study, Cohen’s study team first created standardized brain injuries in mice, and one week later compared the animals’ conditioned fear response to that of uninjured mice. A week after receiving a mild electric shock in a specific cage, normal mice tend to “freeze” when placed in the same cage, anticipating another shock. The brain-injured mice demonstrated fewer freezing responses—a sign that they had partially lost that piece of learning.
On the other hand, brain-injured mice that received a diet of BCAAs showed the same normal response as the uninjured mice. The BCAA cocktail had restored their learning ability.
In addition to the behavioral results, the team conducted electrophysiological experiments in slices of hippocampus from brain-injured and non-injured mice, and showed that BCAA restored a normal balance of neural activity. “The electrophysiological results were consistent with what we saw in the animals’ functional recovery,” said Cohen.
Although much work remains to be done to translate the finding into a therapy, Cohen expects to collaborate over the next year with other researchers in an early-phase clinical trial of dietary BCAAs in patients with mild to moderate TBI.
The National Institutes of Health provided funding for this study. Cohen’s co-authors were Jeffrey Cole, Ph.D., Christina M. Mitala, Ph.D., Suhali Kundu and Itzhak Nissim, Ph.D., all of Children’s Hospital; Jaclynn A. Elkind of the University of Pennsylvania; and Ajay Verma, M.D., Ph.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md. Cohen and Nissim are also on the faculty of the University of Pennsylvania School of Medicine.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; Chester County Hospital; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.