Propofol Anesthesia Alters Spatial and Topologic Organization of Rat Brain Metabolism.

Abstract

Loss of consciousness during anesthesia reduces local and global rate of cerebral glucose metabolism. Despite this, the influence of gradual anesthetic-induced changes on consciousness across the entire brain metabolic network has barely been studied. The purpose of the present study was to identify specific cerebral metabolic patterns characteristic of different consciousness/anesthesia states induced by intravenous anesthetic propofol. At various times, 20 Sprague-Dawley adult rats were intravenously administered three different dosages of propofol to induce different anesthetic states: mild sedation (20 mg · kg · h), deep sedation (40 mg · kg · h), and deep anesthesia (80 mg · kg · h). Using [F]fluorodeoxyglucose positron emission tomography brain imaging, alterations in the spatial pattern of metabolic distribution and metabolic topography were investigated by applying voxel-based spatial covariance analysis and graph-theory analysis. Evident reductions were found in baseline metabolism along with altered metabolic spatial distribution during propofol-induced anesthesia. Moreover, graph-theory analysis revealed a disruption in global and local efficiency of the metabolic brain network characterized by decreases in metabolic connectivity and energy efficiency during propofol-induced deep anesthesia (mild sedation global efficiency/local efficiency = 0.6985/0.7190, deep sedation global efficiency/local efficiency = 0.7444/0.7875, deep anesthesia global efficiency/local efficiency = 0.4498/0.6481; mild sedation vs. deep sedation, global efficiency: P = 0.356, local efficiency: P = 0.079; mild sedation vs. deep anesthesia, global efficiency: P < 0.0001, local efficiency: P < 0.0001; deep sedation vs. deep anesthesia, global efficiency: P < 0.0001, local efficiency: P < 0.0001). A strong spatial correlation was also found between cerebral metabolism and metabolic connectivity strength, which decreased significantly with deepening anesthesia level (correlation coefficients: mild sedation, r = 0.55, deep sedation, r = 0.47; deep anesthesia, r = 0.23; P < 0.0001 between the sedation and deep anesthesia groups). The data revealed anesthesia-related alterations in spatial and topologic organization of metabolic brain network, as well as a close relationship between metabolic connectivity and cerebral metabolism during propofol anesthesia. These findings may provide novel insights into the metabolic mechanism of anesthetic-induced loss of consciousness.