Propofol rather than Isoflurane Accelerates the Interstitial Fluid Drainage in the Deep Rat Brain

Objective: Different anesthetics have distinct effects on the interstitial fluid (ISF) drainage in the extracellular space (ECS) of the superficial rat brain, while their effects on ISF drainage in the ECS of the deep rat brain still remain unknown. Herein, we attempt to investigate and compare the effects of propofol and isoflurane on ECS structure and ISF drainage in the caudate-putamen (CPu) and thalamus (Tha) of the deep rat brain. Methods: Adult Sprague-Dawley rats were anesthetized with propofol or isoflurane, respectively. Twenty-four anesthetized rats were randomly divided into the propofol-CPu, isoflurane-CPu, propofol-Tha, and isoflurane-Tha groups. Tracer-based magnetic resonance imaging (MRI) and fluorescent-labeled tracer assay were utilized to quantify ISF drainage in the deep brain. Results: The half-life of ISF in the propofol-CPu and propofol-Tha groups was shorter than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. The ECS volume fraction in the propofol-CPu and propofol-Tha groups was much higher than that in the isoflurane-CPu and isoflurane-Tha groups, respectively. However, the ECS tortuosity in the propofol-CPu and propofol-Tha groups was much smaller than that in isoflurane-CPu and isoflurane-Tha groups, respectively. Conclusions: Our results demonstrate that propofol rather than isoflurane accelerates the ISF drainage in the deep rat brain, which provides novel insights into the selective control of ISF drainage and guides selection of anesthetic agents in different clinical settings, and unravels the mechanism of how general anesthetics function.