Faculty Collaboration Database

Sleep loss, caffeine, sleep aids and sedation modify brain abnormalities of mild traumatic brain injury. Exp Neurol 2024 Feb;372:114620

Date

11/30/2023

Pubmed ID

38029810

DOI

10.1016/j.expneurol.2023.114620

Scopus ID

2-s2.0-85179070318 (requires institutional sign-in at Scopus site)

Abstract

Little evidence exists about how mild traumatic brain injury (mTBI) is affected by commonly encountered exposures of sleep loss, sleep aids, and caffeine that might be potential therapeutic opportunities. In addition, while propofol sedation is administered in severe TBI, its potential utility in mild TBI is unclear. Each of these exposures is known to have pronounced effects on cerebral metabolism and blood flow and neurochemistry. We hypothesized that they each interact with cerebral metabolic dynamics post-injury and change the subclinical characteristics of mTBI. MTBI in rats was produced by head rotational acceleration injury that mimics the biomechanics of human mTBI. Three mTBIs spaced 48 h apart were used to increase the likelihood that vulnerabilities induced by repeated mTBI would be manifested without clinically relevant structural damage. After the third mTBI, rats were immediately sleep deprived or administered caffeine or suvorexant (an orexin antagonist and sleep aid) for the next 24 h or administered propofol for 5 h. Resting state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) were performed 24 h after the third mTBI and again after 30 days to determine changes to the brain mTBI phenotype. Multi-modal analyses on brain regions of interest included measures of functional connectivity and regional homogeneity from rs-fMRI, and mean diffusivity (MD) and fractional anisotropy (FA) from DTI. Each intervention changed the mTBI profile of subclinical effects that presumably underlie healing, compensation, damage, and plasticity. Sleep loss during the acute post-injury period resulted in dramatic changes to functional connectivity. Caffeine, propofol sedation and suvorexant were especially noteworthy for differential effects on microstructure in gray and white matter regions after mTBI. The present results indicate that commonplace exposures and short-term sedation alter the subclinical manifestations of repeated mTBI and therefore likely play roles in symptomatology and vulnerability to damage by repeated mTBI.

Author List

Everson CA, Szabo A, Plyer C, Hammeke TA, Stemper BD, Budde MD

Authors

Matthew Budde PhD Associate Professor in the Neurosurgery department at Medical College of Wisconsin
Carol 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 Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Brain
Brain Concussion
Caffeine
Diffusion Tensor Imaging
Humans
Propofol
Rats
Sleep
White Matter