In vivo assessment of the influence of general anesthetics on transmembrane water cycling in the brain

This study presents the first in vivo measurement of transcytolemmal water exchange in the brain using a novel Magnetic Resonance technique. We extend previous applications of Chemical Exchange Saturation Transfer (CEST) to examine water exchange across cellular membranes in late-stage chicken embryo brains. The immature blood-brain barrier at this stage allows Gadolinium-Based Contrast Agents (GBCAs) to penetrate the brain's interstitial space, sensitizing the CEST effect to water exchange between intra- and extracellular environments. Exchange rates were measured in the awake brain and under different anaesthetic regimens, including isoflurane and ketamine/xylazine. Results show that brain water exchange is dominated by activity-dependent mechanisms, with anaesthesia reducing exchange rates by over an order of magnitude. These findings suggest that anaesthetics may impact neuronal and glial function by interfering with active transport mechanisms, potentially altering brain water homeostasis. This study highlights the utility of CEST MRI for studying dynamic biological processes in vivo.