Effects of traumatic brain injury (TBI) on hypocretin neurons and sleep of mice

Disorders of sleep and wakefulness have been reported in up to 73% individuals who have experienced traumatic brain injury (TBI). Specifically, increased sleep need and excessive daytime sleepiness are often reported post-TBI. The etiology of post-TBI sleep disturbances is not well understood, and current pharmacological therapies have limited efficacy. Here, we investigate the effects of TBI on sleep-wake behavior and on hypocretin (Hcrt) and melanin-concentrating hormone (MCH), two neuropeptides important for regulating sleep and wakefulness. Adult male C57BL/6J mice ( n  = 6–10/group) were implanted with EEG recording electrodes and baseline recordings were obtained. TBI was then induced using controlled cortical impact (CCI). EEG recordings were obtained from the same animals at 7 and 15 days post-surgery. Another group of animals ( n  = 6–8/group) underwent sham or TBI surgery and was sacrificed 7 or 15 days later. Brains from these animals were used for immunohistochemistry to determine the number of Hcrt- or MCH-producing neurons in the hypothalamus. At 15 days post-surgery, wakefulness was decreased and NREM sleep was increased during the dark period in moderately injured animals. Moderate injury resulted in significantly fewer Hcrt-producing neurons. There were no significant differences among groups in MCH-producing neurons. Because Hcrt is an important promoter of wakefulness, the decrease in number of Hcrt-producing neurons may be one mechanism underlying the observed decrease in wakefulness and increase in NREM sleep after TBI.