Mid-Atlantic Consortium Newsletter Summer 2013

Amino Acid Supplements Could Repair Brain Injury

Boy hit in head by soccer ballA treatment developed at the Children’s Hospital of Philadelphia (CHOP) and proven to restore cognitive abilities in mice with traumatic brain injuries will soon be tested in college athletes who have sustained concussions.

Traumatic brain injury (TBI) can result from any head injury, and the consequences can vary substantially in their severity and the pattern of abilities that are affected. When TBI occurs during childhood, it can result in developmental disability. There are no current remedies for losses in memory, learning and other brain functions caused by TBI, which also makes the brain more susceptible to seizures.

The new treatment consists of a cocktail of three, branched-chain amino acids (BCAAs) —leucine, isoleucine and valine—designed to help restore an imbalance of neurochemicals caused by TBI. The therapy has been tested successfully in mouse models of TBI in the lab of Akiva Cohen, Ph.D., associate professor of neurology, neurosurgery and pediatrics at the University of Pennsylvania’s Perelman School of Medicine, and CHOP.

In their studies, Cohen and his colleagues created standardized brain injuries in mice, and one week later compared the animals’ learning 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 mice are not injured with this method, but they readily learn this conditioned fear response. Brain-injured mice demonstrate fewer freezing responses—a sign that their learning is impaired.

Cohen’s studies found that brain-injured mice treated with BCAAs for five days showed the same normal response as uninjured mice during the learning test. Other investigations of the animals’ brains also showed BCAAs restored a normal balance of activity.

Based on mouse results, Cohen and his colleagues at the medical school are planning a clinical trial, to begin in the next two to three months, to test an oral supplement version of the amino acid therapy in college athletes who have had concussions. The work is funded by the Dana Foundation.

BCAAs are needed to produce 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 send signals to other nerve cells, while GABA inhibits this “firing.” With too much excitement or too little, the brain doesn’t work properly.

TBI can upset glutamate–GABA balance, often leading to damage to thee hippocampus, a brain structure involved in higher learning and memory. Cohen’s studies have affirmed that such injuries reduce levels of BCAAs, further supporting the rationale for the newly proposed treatment.

 

For more information about Cohen’s work, see http://www.research.chop.edu/programs/cohenlab/index.php. A video about the BCAA work can be seen at http://www.jove.com/video/4411?status=a6417k.

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