Influence of different isoflurane anesthesia protocols on murine cerebral hemodynamics measured with pseudo‐continuous arterial spin labeling

Abstract

Arterial spin labeling (ASL)‐MRI can noninvasively map cerebral blood flow (CBF) and cerebrovascular reactivity (CVR), potential biomarkers of cognitive impairment and dementia. Mouse models of disease are frequently used in translational MRI studies, which are commonly performed under anesthesia. Understanding the influence of the specific anesthesia protocol used on the measured parameters is important for accurate interpretation of hemodynamic studies with mice. Isoflurane is a frequently used anesthetic with vasodilative properties. Here, the influence of three distinct isoflurane protocols was studied with pseudo‐continuous ASL in two different mouse strains. The first protocol was a free‐breathing set‐up with medium concentrations, the second a free‐breathing set‐up with low induction and maintenance concentrations, and the third a set‐up with medium concentrations and mechanical ventilation. A protocol with the vasoconstrictive anesthetic medetomidine was used as a comparison. As expected, medium isoflurane anesthesia resulted in significantly higher CBF and lower CVR values than medetomidine (median whole‐brain CBF of 157.7 vs 84.4 mL/100 g/min and CVR of 0.54 vs 51.7% in C57BL/6 J mice). The other two isoflurane protocols lowered the CBF and increased the CVR values compared with medium isoflurane anesthesia, without obvious differences between them (median whole‐brain CBF of 138.9 vs 131.7 mL/100 g/min and CVR of 10.0 vs 9.6%, in C57BL/6 J mice). Furthermore, CVR was shown to be dependent on baseline CBF, regardless of the anesthesia protocol used.

Cerebral blood flow and cerebrovascular reactivity are preserved in a mouse model of cerebral microvascular amyloidosis

“…Therefore, additional experiments were performed to determine whether differences in experimental design could explain this discrepancy. A likely candidate was the difference in anesthesia protocol, as this has been shown to significantly influence CVR experiments ( Petrinovic et al, 2016 ; Munting et al, 2019 ). Another likely candidate was the difference in imaging modality, as ASL-MRI and LDF are sensitive to different blood components, namely flux of blood plasma (ASL-MRI) or velocity of red blood cells (LDF).…”

“…Animal preparation – the isoflurane anesthesia protocol during the first four imaging sessions in cohort 1 was similar to the ‘low isoflurane protocol’ as described in Munting et al, 2019 . In this protocol, the isoflurane concentration is kept low both during induction (2.0% for 5 min) and maintenance (1.25%), to limit the vasodilatory effects of the anesthetic, which would impact the reactivity measurements.…”

“…The coronal slice package with 21 slices was additionally used for quantification of the brain volume. The pCASL scan protocol was similar as in Munting et al, 2019 . In short, the phase of the pCASL labeling was first optimized using pre-scans ( Hirschler et al, 2018b ).…”

Peripheral electrical stimulation augments cerebral collateral circulation if performed within a critical time window

“…Isoflurane has a well-documented effect on cerebral blood flow 15,[26][27][28] . However, since this study was focused on relative changes in cerebral blood flow with each animal acting as its own control, the absolute effects of isoflurane should be less of an issue.…”

“…However, since this study was focused on relative changes in cerebral blood flow with each animal acting as its own control, the absolute effects of isoflurane should be less of an issue. Regardless, a low-dose isoflurane protocol, as described in Munting et al was utilized as their study demonstrated that this particular isoflurane protocol appeared to be have the least effect on cerebral blood flow while maintaining cerebrovascular reactivity 26 . For imaging sessions, mice were anesthetized with isoflurane (2% induction for no greater than 5 minutes with 1.25% maintenance) in oxygen and affixed to a stereotaxic frame.…”