microGLYMPH: a conceptual translational roadmap for microdialysis‑based assessment of CSF-interstitial solute...

The glymphatic system facilitates cerebrospinal fluid (CSF)-interstitial fluid exchange and plays a key role in solute clearance and neurophysiological homeostasis. While dysfunction of this system has been shown in traumatic brain injury, stroke, meningitis, idiopathic normal pressure hydrocephalus and neurodegenerative diseases, direct measurement of glymphatic transport in humans remains elusive. We propose microGLYMPH as a translational, hypothesis-generating framework that combines established clinical cerebral microdialysis with controlled CSF tracer administration via existing clinical access routes, including an external ventricular drain, cisternal access during surgery, or lumbar intrathecal injection when clinically justified. The aim is to obtain time-resolved regional tracer profiles in microdialysate and to interpret these alongside arousal state, intracranial dynamics, and, where available, complementary imaging, thereby providing an indirect measure of CSF-interstitial exchange kinetics and peripheral tracer appearance. We further define the key design, analytical and practical limitations that must be resolved before the approach can extend beyond exploratory use, notably catheter-adjacent effects, blood-brain barrier disruption, drainage practices, and the intrinsically focal nature of microdialysis. microGLYMPH is therefore intended as a staged roadmap for first-in-human feasibility studies and subsequent hypothesis-driven investigations of neurofluid solute transport after acute brain injury.