Biomarkers of Traumatic Injury Are Transported from Brain to Blood via the Glymphatic System

TLDR

Traumatic brain injury presents with nonspecific symptoms, prompting a search for blood biomarkers, yet the mechanism by which brain‑derived cytosolic proteins reach peripheral blood remains unclear. In a mouse TBI model, glymphatic CSF flow delivers biomarkers to blood, and interventions that alter glymphatic activity—such as sleep deprivation or cisternotomy—reduce or abolish serum increases in S100β, GFAP, and NSE, suggesting that routine TBI care may impair biomarker utility.

Abstract

The nonspecific and variable presentation of traumatic brain injury (TBI) has motivated an intense search for blood-based biomarkers that can objectively predict the severity of injury. However, it is not known how cytosolic proteins released from traumatized brain tissue reach the peripheral blood. Here we show in a murine TBI model that CSF movement through the recently characterized glymphatic pathway transports biomarkers to blood via the cervical lymphatics. Clinically relevant manipulation of glymphatic activity, including sleep deprivation and cisternotomy, suppressed or eliminated TBI-induced increases in serum S100β, GFAP, and neuron specific enolase. We conclude that routine TBI patient management may limit the clinical utility of blood-based biomarkers because their brain-to-blood transport depends on glymphatic activity.