Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury.
Coma and chronic sleepiness are common after traumatic brain injury (TBI). Here, we explored whether injury to arousal-promoting brainstem neurons occurs in patients with fatal TBI.



Postmortem examination of 8 TBI patients and 10 controls.



Compared to controls, TBI patients had 17% fewer serotonergic neurons in the dorsal raphe nucleus (effect size: 1.25), but the number of serotonergic neurons did not differ in the median raphe nucleus. TBI patients also had 29% fewer noradrenergic neurons in the locus coeruleus (effect size: 0.96). The number of cholinergic neurons in the pedunculopontine and laterodorsal tegmental nuclei (PPT/LDT) was similar in TBI patients and controls.



TBI injures arousal-promoting neurons of the mesopontine tegmentum, but this injury is less severe than previously observed in hypothalamic arousal-promoting neurons. Most likely, posttraumatic arousal disturbances are not primarily caused by damage to these brainstem neurons, but arise from an aggregate of injuries, including damage to hypothalamic arousal nuclei and disruption of other arousal-related circuitries.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.|Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.
Philipp O
PO
Valko
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.|Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.|Department of General Pathology and Pathological Physiology, Institute of Experimental Medicine, St.Petersburg, Russia.
Yuri V
YV
Gavrilov
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
Mihoko
M
Yamamoto
Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.
Daniela
D
Noaín
Department of Neuropathology, Beth Israel Deaconess Medical Center, Boston, MA.
Hasini
H
Reddy
Department of Neuropathology, Institute of Pathology, Medical University of Graz, Austria.
Johannes
J
Haybaeck
Department of Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Kepler University Hospital, Johannes Kepler University of Linz, Austria.
Serge
S
Weis
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.|Department of Neurology, University Hospital Zurich, University of Zurich, Switzerland.
Christian R
CR
Baumann
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA.
Thomas E
TE
Scammell
D059331:Adrenergic Neurons / Q000473:pathology; D001143:Arousal; D001344:Autopsy; D000070642:Brain Injuries, Traumatic / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology*; D016022:Case-Control Studies; D059329:Cholinergic Neurons / Q000166:cytology; D065847:Dorsal Raphe Nucleus / Q000473:pathology; D006801:Humans; D007031:Hypothalamus / Q000473:pathology; D008125:Locus Coeruleus / Q000473:pathology; D009434:Neural Pathways; D009474:Neurons / Q000166:cytology / Q000473:pathology*; D011149:Pons / Q000166:cytology; D059326:Serotonergic Neurons / Q000166:cytology / Q000473:pathology
arousal; coma; locus coeruleus; raphe nucleus; traumatic brain injury