Differential Alterations to the Metabolic Connectivity of the Cortical and Subcortical Regions in Rat Brain During Ketamine-Induced Unconsciousness.

Ketamine anesthesia increased glucose metabolism across most brain regions in rats, but reduced metabolic connectivity and network efficiency in the cortex while increasing them in subcortical regions. The study used FDG-PET imaging on 20 adult rats given saline (awake), low-dose ketamine (subanesthesia), and high-dose ketamine (anesthesia). Graph-theory analysis showed that during ketamine anesthesia, global efficiency decreased in the cortex and increased in the subcortex compared to the awake state. These changes in cortical metabolic networks may help explain how general anesthesia induces loss of consciousness.

Study at a glance

Abstract

Ketamine anesthesia increased glucose metabolism in most brain regions compared to another intravenous anesthetic propofol. However, whether the changes in cerebral metabolic networks induced by ketamine share the same mechanism with propofol remains to be explored. The purpose of the present study was to identify specific features of metabolic network in rat brains during ketamine-induced subanesthesia state and anesthesia state compared to awake state. We acquired fluorodeoxyglucose positron emission tomography (FDG-PET) images in 20 healthy adult Sprague-Dawley rats that were intravenously administrated saline and ketamine to achieve different conscious states: awake (normal saline), subanesthesia (30 mg kg -1 h -1 ), and anesthesia (160 mg kg -1 h -1 ). Based on the FDG-PET data, the alterations in cerebral glucose metabolism and metabolic topography were investigated by graph-theory analysis. The baseline metabolism in rat brains was found significantly increased during ketamine-induced subanesthesia and anesthesia. The graph-theory analysis manifested a reduction in metabolism connectivity and network global/local efficiency across cortical regions and an increase across subcortical regions during ketamine-induced anesthesia (nonparametric permutation test: global efficiency between awake and anesthesia, cortex: P = .016, subcortex: P = .015; global efficiency between subanesthesia and anesthesia, subcortex: P = .012). Ketamine broadly increased brain metabolism alongside decreased metabolic connectivity and network efficiency of cortex network. Modulation of these cortical metabolic networks may be a candidate mechanism underlying general anesthesia-induced loss of consciousness.