Damage to Arousal-Promoting Brainstem Neurons with Traumatic Brain Injury

Valko, Philipp O. ; Gavrilov, Yuri V. ; Yamamoto, Mihoko ; Noaín, Daniela ; Reddy, Hasini ; Haybaeck, Johannes ; Weis, Serge ; Baumann, Christian R. ; Scammell, Thomas E.

In: Sleep, 2016, vol. 39, no. 6, p. 1249-1252

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    Summary
    Abstract Study Objectives: 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. Methods: Postmortem examination of 8 TBI patients and 10 controls. Results: 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. Conclusions: 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. Significance Direct damage to arousal-promoting neurons is one of several potential causes of chronic sleep-wake disturbances after traumatic brain injury (TBI). We measured the degree of cell loss in arousal structures of the brainstem and hypothalamus in subjects with severe TBI. We found mild neuronal loss in the dorsal raphe nucleus and locus coeruleus, and overall, the monoaminergic and cholinergic arousal nuclei in the rostral brainstem appeared less injured than the arousal structures in the dorsal hypothalamus. The location of these nuclei and local tissue characteristics may better protect these neurons from contusions, shearing, and other trauma-induced forces than those in the hypothalamus.