title: Novel Rat Model of Weight Drop-Induced Closed Diffuse Traumatic Brain Injury Compatible with Electrophysiological Recordings of Vigilance States.
abstract: Traumatic brain injury (TBI) is a major cause of persistent disabilities such as sleep-wake disorders (SWD). Rodent studies of SWD after TBI are scarce, however, because of lack of appropriate TBI models reproducing acceleration-deceleration forces and compatible with electroencephalography/myography (EEG/EMG)-based recordings of vigilance states. We therefore adapted the Marmarou impact acceleration model to allow for compatibility with EEG-headset implantation. After implantation of EEG/EMG electrodes, we induced closed TBI by a frontal, angular hit with a weight-drop device (56 rats, weight 2500 g, fall height 25 cm). Subsequently, we tested our model's usefulness for long-term studies on a behavioral, electrophysiological, and histological level. Neurological, motor, and memory deficits were assessed with the neurological severity score, open field, and novel object recognition tests, respectively. EEG/EMG recordings were performed in both Sham (n = 7) and TBI (n = 7) rats before and 1, 7, and 28 days after trauma to evaluate sleep-wake proportions and post-traumatic implant stability. Histological assessments included hematoxylin and eosin staining for parenchymal damage and hemorrhage and amyloid precursor protein staining for diffuse axonal damage. All rats survived TBI without major neurological or motor deficits. Memory function was impaired after TBI at weeks 1, 2, and 3 and recovered at week 4. EEG implants were stable for at least 1 month and enabled qualitative and quantitative sleep analyses. Histological assessments revealed no major bleedings or necrosis but intense diffuse axonal damage after TBI. This approach fulfills major pre-conditions for experimental TBI models and offers a possibility to electrophysiologically study behavioral states before and after trauma.
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .
authors.forename: Fabian
authors.initials: F
authors.lastname: Büchele
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .|2 Neuroscience Centre Zurich ZNZ, University of Zurich , Zurich, Switzerland .
authors.forename: Marta M
authors.initials: MM
authors.lastname: Morawska
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .
authors.forename: Sebastian R
authors.initials: SR
authors.lastname: Schreglmann
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .
authors.forename: Marco
authors.initials: M
authors.lastname: Penner
authors.affiliation: 3 Working Group on Accident Mechanics, Swiss Federal Institute of Technology , Zurich, Switzerland .
authors.forename: Markus
authors.initials: M
authors.lastname: Muser
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .
authors.forename: Christian R
authors.initials: CR
authors.lastname: Baumann
authors.affiliation: 1 Department of Neurology, University Hospital of Zurich , Zurich, Switzerland .
authors.forename: Daniela
authors.initials: D
authors.lastname: Noain
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D020833:Diffuse Axonal Injury / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D012720:Severity of Illness Index
keywords: TBI; rat model; sleep recording; traumatic axonal injury; weight drop