title: Sleep Modulation Alleviates Axonal Damage and Cognitive Decline after Rodent Traumatic Brain Injury.
abstract: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. It produces diffuse axonal injury (DAI), which contributes to cognitive impairment, but effective disease-modifying treatment strategies are missing. We have recently developed a rat model of closed skull TBI that reproduces human TBI consequences, including DAI and clinical sequelae such as memory impairment. Here, we investigated whether sleep modulation after trauma has an impact on DAI and memory outcome. We assessed cognition with the novel object recognition test and stained for amyloid precursor protein, a DAI marker. We found that both sleep induction and restriction acutely after TBI enhanced encephalographic slow-wave activity, markedly reduced diffuse axonal damage in the cortex and hippocampus, and improved memory impairment 2 weeks after trauma. These results suggest that enhancing slow-wave sleep acutely after trauma may have a beneficial disease-modifying effect in subjects with acute TBI.
  
  
  CONCLUSIONS
  Traumatic brain injury (TBI) is a clinically important entity. Cognitive deficits belong to the most prevalent chronic posttraumatic symptoms, most likely due to diffuse axonal injury (DAI). A growing body of evidence suggests a role of sleep in the clearance of waste products in the brain, possibly including amyloid precursor protein (APP), a marker of DAI. In this study, we provide evidence that enhancement of slow-wave oscillatory activity in the delta-frequency range decreases the APP-immunoreactivity and preserves cognitive abilities after trauma, potentially offering novel, noninvasive treatment options for traumatic injury.
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland marta.morawska@usz.ch.
authors.forename: Marta M
authors.identifier: http://orcid.org/0000-0003-1612-6786
authors.initials: MM
authors.lastname: Morawska
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Büchele
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Carlos Goncalves
authors.initials: CG
authors.lastname: Moreira
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Lukas L
authors.initials: LL
authors.lastname: Imbach
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Noain
authors.affiliation: Department of Neurology, University Hospital of Zurich, 8091 Zurich, Switzerland.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Baumann
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000503:physiopathology* / Q000534:rehabilitation*; D060825:Cognitive Dysfunction / Q000209:etiology / Q000503:physiopathology / Q000534:rehabilitation; D003700:Delta Rhythm; D020833:Diffuse Axonal Injury / Q000209:etiology / Q000503:physiopathology* / Q000534:rehabilitation*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology* / Q000534:rehabilitation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012894:Sleep Stages
keywords: diffuse axonal damage; memory; sleep; traumatic brain injury