Sleep‐wake characteristics in a mouse model of severe traumatic brain injury: Relation to posttraumatic epilepsy

• Published in: Epilepsia open Vol. 6; no. 1; pp. 181 - 194
• Main Authors: Konduru, Sai Sruthi, Wallace, Eli P., Pfammatter, Jesse A., Rodrigues, Paulo V., Jones, Mathew V., Maganti, Rama K.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-03-2021; John Wiley and Sons Inc; Wiley
• Subjects: Animals; Biomarkers; Brain; Brain Injuries, Traumatic - complications; Convulsions & seizures; Disease Models, Animal; Electrodes; Electroencephalography; Electromyography; Epilepsy; Epilepsy, Post-Traumatic - etiology; Full‐length Original Research; Laboratory animals; Male; Mice; NREM delta power; Post traumatic stress disorder; posttraumatic epilepsy; Sleep; sleep spindles; Sleep Wake Disorders - etiology; sleep‐wake disturbances; Stainless steel; Tomography, X-Ray Computed; Traumatic brain injury; United States > US; NREM delta power; sleep spindles; Traumatic brain injury; sleep‐wake disturbances; posttraumatic epilepsy
• ISSN: 2470-9239; 2470-9239
• DOI: 10.1002/epi4.12462

Study objectives
Traumatic brain injury (TBI) results in sequelae that include posttraumatic epilepsy (PTE) and sleep‐wake disturbances. Here, we sought to determine whether sleep characteristics could predict development of PTE in a model of severe TBI.
Methods
Following controlled cortical impact (CCI) or sham injury (craniotomy only), CD‐1 mice were implanted with epidural electroencephalography (EEG) and nuchal electromyography (EMG) electrodes. Acute (1st week) and chronic (months 1, 2, or 3) 1‐week‐long video‐EEG recordings were performed after the injury to examine epileptiform activity. High‐amplitude interictal events were extracted from EEG using an automated method. After scoring sleep‐wake patterns, sleep spindles and EEG delta power were derived from nonrapid eye movement (NREM) sleep epochs. Brain CTs (computerized tomography) were performed in sham and CCI cohorts to quantify the brain lesions. We then employed a no craniotomy (NC) control to perform 1‐week‐long EEG recordings at week 1 and month 1 after surgery.
Results
Posttraumatic seizures were seen in the CCI group only, whereas interictal epileptiform activity was seen in CCI or sham. Sleep‐wake disruptions consisted of shorter wake or NREM bout lengths and shorter duration or lower power for spindles in CCI and sham. NREM EEG delta power increased in CCI and sham groups compared with NC though the CCI group with posttraumatic seizures had lower power at a chronic time point compared with those without. Follow‐up brain CTs showed a small lesion in the sham injury group suggesting a milder form of TBI that may account for their interictal activity and sleep changes.
Significance
In our TBI model, tracking changes in NREM delta power distinguishes between CCI acutely and animals that will eventually develop PTE, but further work is necessary to identify sleep biomarkers of PTE. Employing NC controls together with sham controls should be considered in future TBI studies.