Fasting prevents medetomidine‐induced hyperglycaemia and alterations of neurovascular coupling in the somatosensory cortex of the rat during noxious stimulation

Abstract

Medetomidine and isoflurane are commonly used for general anaesthesia in fMRI studies, but they alter cerebral blood flow (CBF) regulation and neurovascular coupling (NVC). In addition, medetomidine induces hypoinsulinemia and hyperglycaemia, which also alter CBF regulation and NVC. Furthermore, sudden changes in arterial pressure induced by noxious stimulation may affect NVC differently under medetomidine and isoflurane anaesthesia, considering their different effects on vascular functions. The first objective of this study was to compare NVC under medetomidine and isoflurane anaesthesia during noxious stimulation. The second objective was to examine whether fasting may improve NVC by reducing medetomidine‐induced hyperglycaemia. In male Wister rats, noxious electrical stimulation was applied to the sciatic nerve in fasted or non‐fasted animals. CBF and local field potentials (LFP) were recorded in the somatosensory cortex to assess NVC (CBF/LFP ratio). The CBF/LFP ratio was increased by medetomidine compared with isoflurane (p = 0.004), but this effect was abolished by fasting (p = 0.8). Accordingly, medetomidine produced a threefold increase in blood glucose (p < 0.001), but this effect was also abolished by fasting (p = 0.3). This indicates that isoflurane and medetomidine anaesthesia alter NVC differently, but the undesirable glucose dependent effects of medetomidine on NVC can be prevented by fasting.

Translational Magnetic Resonance Imaging in Autism Spectrum Disorder From the Mouse Model to Human

“…These results indicate that low-dose anesthesia can be useful to investigate the abnormality of the functional network in resting state, although the limitation of interpretation of fMRI under light anesthesia still exists. Despite common functional connectivity between awaked and lightly anesthetized state ( Grandjean et al, 2020 ; Tsurugizawa and Yoshimaru, 2021 ), fMRI signal changes to the physiological stimuli are significantly disturbed by the anesthetic ( Peeters et al, 2001 ; Tsurugizawa et al, 2010 , 2016 ; Aksenov et al, 2015 ; Tokunaga et al, 2021 ; You et al, 2021 ). As an alternative, awake mouse fMRI is developed using habituation training to reduce stress during MRI experiments ( Tsurugizawa et al, 2013 , 2020 , 2021 ; Bergmann et al, 2016 ; Yoshida et al, 2016 ; Madularu et al, 2017 ; Chen et al, 2020 ; Russo et al, 2021 ).…”