Reduced glymphatic function after traumatic brain injury measured using diffusion MRI

Abstract

The glymphatic system is a perivascular fluid clearance system, most active during sleep, considered important for clearing the brain of waste products and toxins. Glymphatic failure is hypothesized to underlie brain protein deposition in neurodegenerative disorders like Alzheimers Disease. Preclinical evidence suggests that a functioning glymphatic system is also essential for recovery from traumatic brain injury (TBI), which involves release of debris and toxic proteins that need to be cleared from the brain. We estimated glymphatic clearance using Diffusion Tensor Imaging Along Perivascular Spaces (DTI-ALPS), an MRI-derived measure of water diffusivity surrounding veins, in 13 non-injured controls and 37 subjects with TBI (~5 months post). We additionally measured plasma concentrations of Neurofilament light chain (NfL), a biomarker of injury severity, in a subset of subjects. DTI-ALPS was significantly lower in TBI subjects compared to controls, after controlling for age, and significantly, negatively correlated with NfL. Glymphatic impairment after TBI could be due to mechanisms such as mis-localization of glymphatic water channels, inflammation, proteinopathy and/or sleep disruption. Additional work, including longitudinal studies, are needed to confirm results and assess glymphatic associations with outcome. Understanding post-TBI glymphatic functioning could inform novel therapies to improve short-term recovery and reduce later risk of neurodegeneration.