LAUSR

OBJECTIVE Alfaxalone has been used increasingly in biomedical research and medication of large animal anesthesia in recent years. However, its effects on the cerebral blood flow (CBF) physiology and intrinsic neuronal activity of anesthetized brains during neuroimaging study remain poorly understood. METHODS Four healthy adult rhesus monkeys were anesthetized initially with alfaxalone (0.125 mg/kg/min) or ketamine (1.6 mg/kg/min) for 50 min, then administrated with 0.8% isoflurane for 60 min. Heart rates, breathing beats, and blood pressures were continuously monitored. CBF data was collected using pseudo-continuous arterial spin-labeling (pCASL) MRI technique and rsfMRI data were collected using single-shot EPI sequence for each anesthetic. RESULTS Both the heart rates and mean arterial pressure (MAP) remained more stable during the alfaxalone infusion than those seen during ketamine administration. Alfaxalone reduced CBF substantially compared to ketamine anesthesia (grey matter, 65 ± 22 vs 179 ± 38 ml/100 g/min, p < 0.001; white matter, 14 ± 7 vs 26 ± 6 ml/100 g/min, p < 0.05); In addition, general CBF increase was seen in all selected cortical and subcortical regions of alfaxalone-pretreated monkey brains during isoflurane exposure, very different from the findings in isoflurane-exposed monkeys pretreated with ketamine. Also, alfaxalone showed similar suppression effects on functional connectivity of the monkey brain as ketamine. CONCLUSION Alfaxalone showed strong suppression effects on CBF of the monkey brain.The residual effect of alfaxalone on CBF of isoflurane-exposed brains was monotonous when used as induction agent for inhalational anesthesia. In particular, alfaxalone resulted in stable physiological readings when used alone or as induction agent and showed similar suppression effect on intrinsic neuronal activity of the brain in comparison with ketamine. These findings suggest alfaxalone can be a good alternative to veterinary anesthesia in examination of brain physiology and functionality of large animal models in which CBF and functional connectivity are critical measures to characterize the brain lesion evolution and functional alteration and recovery.