Subclinical brain manifestations of repeated mild traumatic brain injury are changed by chronic exposure to sleep loss, caffeine, and sleep aids. Exp Neurol 2024 Nov;381:114928
Date
08/22/2024Pubmed ID
39168169DOI
10.1016/j.expneurol.2024.114928Scopus ID
2-s2.0-85201764724 (requires institutional sign-in at Scopus site)Abstract
INTRODUCTION: After mild traumatic brain injury (mTBI), the brain is labile for weeks and months and vulnerable to repeated concussions. During this time, patients are exposed to everyday circumstances that, in themselves, affect brain metabolism and blood flow and neural processing. How commonplace activities interact with the injured brain is unknown. The present study in an animal model investigated the extent to which three commonly experienced exposures-daily caffeine usage, chronic sleep loss, and chronic sleep aid medication-affect the injured brain in the chronic phase.
METHODS: Subclinical trauma by repeated mTBIs was produced by our head rotational acceleration injury model, which causes brain injury consistent with the mechanism of concussion in humans. Forty-eight hours after a third mTBI, chronic administrations of caffeine, sleep restriction, or zolpidem (sedative hypnotic) began and were continued for 70 days. On Days 30 and 60 post injury, resting state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were performed.
RESULTS: Chronic caffeine, sleep restriction, and zolpidem each changed the subclinical brain characteristics of mTBI at both 30 and 60 days post injury, detected by different MRI modalities. Each treatment caused microstructural alterations in DTI metrics in the insular cortex and retrosplenial cortex compared with mTBI, but also uniquely affected other gray and white matter regions. Zolpidem administration affected the largest number of individual structures in mTBI at both 30 and 60 days, and not necessarily toward normalization (sham treatment). Chronic sleep restriction changed local functional connectivity at 30 days in diametrical opposition to chronic caffeine ingestion, and both treatment outcomes were different from sham, mTBI-only and zolpidem comparisons. The results indicate that commonly encountered exposures modify subclinical brain activity and structure long after healing is expected to be complete.
CONCLUSIONS: Changes in activity and structure detected by fMRI are widely understood to reflect changes in the functions of the affected region which conceivably underlie mTBI neuropathology and symptomatology in the chronic phase after injury.
Author List
Everson CA, Szabo A, Plyer C, Hammeke TA, Stemper BD, Budde MDAuthors
Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of WisconsinCarol A. Everson PhD Professor in the Medicine department at Medical College of Wisconsin
Brian Stemper PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBrain
Brain Concussion
Caffeine
Central Nervous System Stimulants
Diffusion Tensor Imaging
Magnetic Resonance Imaging
Male
Rats
Rats, Sprague-Dawley
Sleep Aids, Pharmaceutical
Sleep Deprivation
