title: Dietary therapy mitigates persistent wake deficits caused by mild traumatic brain injury.
abstract: Sleep disorders are highly prevalent in patients with traumatic brain injury (TBI) and can significantly impair cognitive rehabilitation. No proven therapies exist to mitigate the neurocognitive consequences of TBI. We show that mild brain injury in mice causes a persistent inability to maintain wakefulness and decreases orexin neuron activation during wakefulness. We gave mice a dietary supplement of branched-chain amino acids (BCAAs), precursors for de novo glutamate synthesis in the brain. BCAA therapy reinstated activation of orexin neurons and improved wake deficits in mice with mild brain injury. Our data suggest that dietary BCAA intervention, acting in part through orexin, can ameliorate injury-induced sleep disturbances and may facilitate cognitive rehabilitation after brain injury.
authors: Division of Sleep Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors: Miranda M
authors: MM
authors: Lim
authors: Jaclynn
authors: J
authors: Elkind
authors: Guoxiang
authors: G
authors: Xiong
authors: Ray
authors: R
authors: Galante
authors: Jingxu
authors: J
authors: Zhu
authors: Lin
authors: L
authors: Zhang
authors: Jie
authors: J
authors: Lian
authors: Julianna
authors: J
authors: Rodin
authors: Nicholas N
authors: NN
authors: Kuzma
authors: Allan I
authors: AI
authors: Pack
authors: Akiva S
authors: AS
authors: Cohen
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000627:therapeutic use; D000818:Animals; D001522:Behavior, Animal; D001930:Brain Injuries / Q000178:diet therapy*; D003071:Cognition; D015928:Cognitive Behavioral Therapy; D004195:Disease Models, Animal; D004569:Electroencephalography; D018698:Glutamic Acid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins; D014851:Wakefulness / Q000502:physiology*
chemical_list: D000597:Amino Acids, Branched-Chain; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018698:Glutamic Acid