Loss of hypocretin (orexin) neurons with traumatic brain injury

Ann Neurol. 2009 Oct;66(4):555-9. doi: 10.1002/ana.21836.


Chronic, daytime sleepiness is a major, disabling symptom for many patients with traumatic brain injury (TBI), but thus far, its etiology is not well understood. Extensive loss of the hypothalamic neurons that produce the wake-promoting neuropeptide hypocretin (orexin) causes the severe sleepiness of narcolepsy, and partial loss of these cells may contribute to the sleepiness of Parkinson disease and other disorders. We have found that the number of hypocretin neurons is significantly reduced in patients with severe TBI. This observation highlights the often overlooked hypothalamic injury in TBI and provides new insights into the causes of chronic sleepiness in patients with TBI.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology*
  • Cell Count / methods
  • Female
  • Humans
  • Hypothalamus / metabolism
  • Hypothalamus / pathology
  • Intracellular Signaling Peptides and Proteins / physiology
  • Male
  • Middle Aged
  • Neurons / metabolism*
  • Neurons / pathology*
  • Neuropeptides / biosynthesis*
  • Neuropeptides / physiology
  • Orexins
  • Pilot Projects
  • Wakefulness / physiology


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins