After suffering a concussion or other traumatic brain injury (TBI), many people (70% or more) experience disturbances in their sleep–wake cycles, such as daytime sleepiness and nighttime insomnia. Such sleep problems can impair attention and memory formation, disrupt quality of life and delay cognitive recovery from TBI. There are currently no proven therapies available to address these sleep disturbances.

Working at University of Pennsylvania (Philadelphia), Miranda Lim and colleagues sought ways to improve these sleep problems by studying a mouse model of mild TBI. Compared with uninjured mice, mice with TBI had a persistent inability to maintain wakefulness and a substantial reduction in activity of orexin-producing neurons when awake (Sci. Transl. Med. 5, 215ra173; 2013). These neurons are involved in maintaining wakefulness in mice and in humans. Orexin has been implicated in narcolepsy and other sleep and arousal disorders in humans, and orexin levels are lower in humans after suffering TBI.

Lim's group next tested whether supplementing the diet with branched-chain amino acids (BCAAs) could restore orexin neuron activity and normalize sleep–wake cycles in mice with TBI. They focused on BCAAs because these compounds are precursors to neurotransmitters and have been shown to increase neural excitability. Although the primary sources of BCAAs in a normal human diet are high-protein foods such as meat and eggs, mice were given BCAAs as a supplement in their drinking water.

Credit: Pete Cruickshank/Alamy

In mice with TBI that were treated with BCAAs, the activity level of orexin neurons returned to normal. Treatment with BCAAs partially reversed the sleep–wake disturbances and restored wakefulness in mice. “These results in an animal model provide a proof-of-principle for investigating this dietary intervention as a treatment for TBI patients,” said Akiva Cohen, a senior author on the study, in a press release. Lim added, “If further research confirms what this study suggests, we could develop a dietary supplement of these amino acids that could be a viable therapy to help people after a concussion.”

BCAAs have been used to treat humans with other diseases, including liver cirrhosis and bipolar disorder, for periods as long as 2 years without adverse effects. They are clinically well tolerated and have only minor side effects. Therefore, BCAA supplementation may hold promise for treating sleep disturbances associated with TBI and thus improving recovery. As Cohen explained, “If a dietary supplement can improve sleeping and waking patterns as well as cognitive problems, it could help brain-injured patients regain crucial functions.”