Disparate volumetric fluid shifts across cerebral tissue compartments with two different anesthetics

Abstract

Background: Large differences in glymphatic system transport—similar in magnitude to those of the sleep/wake cycle—have been observed during anesthesia with dexmedetomidine supplemented with low dose isoflurane (DEXM-I) in comparison to isoflurane (ISO). However, the biophysical and bioenergetic tissue status underlying glymphatic transport differences between anesthetics remains undefined. To further understand biophysical characteristics underlying these differences we investigated volume status across cerebral tissue compartments, water diffusivity, and T2* values in rats anesthetized with DEXM-I in comparison to ISO. Methods: Using a crossover study design, a group of 12 Sprague Dawley female rats underwent repetitive magnetic resonance imaging (MRI) under ISO and DEXM-I. Physiological parameters were continuously measured. MRI included a proton density weighted (PDW) scan to investigate cerebrospinal fluid (CSF) and parenchymal volumetric changes, a multigradient echo scan (MGE) to calculate T2* maps as a measure of ‘bioenergetics’, and a diffusion scan to quantify the apparent diffusion coefficient (ADC). Results: The heart rate was lower with DEXM-I in comparison to ISO, but all other physiological variables were similar across scans and groups. The PDW images revealed a 1% parenchymal volume increase with ISO compared to DEXM-I comprising multiple focal tissue areas scattered across the forebrain. In contrast, with DEXM-I the CSF compartment was enlarged by ~ 6% in comparison to ISO at the level of the basal cisterns and peri-arterial conduits which are main CSF influx routes for glymphatic transport. The T2* maps showed brain-wide increases in T2* in ISO compared to DEXM-I rats. Diffusion-weighted images yielded no significant differences in ADCs across the two anesthesia groups. Conclusions: We demonstrated CSF volume expansion with DEXM-I (in comparison to ISO) and parenchymal (GM) expansion with ISO (in comparison to DEXM-I), which may explain the differences in glymphatic transport. The T2* changes in ISO are suggestive of an increased bioenergetic state associated with excess cellular firing/bursting when compared to DEXM-I.