Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.

The structural basis for glycerol permeation by human AQP7

Human glycerol channel aquaporin 7(AQP7)conducts glycerol release from adipocyte and enters the cells in pancreatic islets,muscles,and kidney tubules,and thus regulates glycerol metabolism in those tissues.Compared with other human aquaglyceroporins,AQP7 shows a less conserved‘‘NPA”motif in the center cavity and a pair of aromatic residues at Ar/R selectivity filter.To understand the structural basis for the glycerol conductance,we crystallized the human AQP7 and determined the structure at 3.7Å.A substrate binding pocket was found near the Ar/R filter where a glycerol molecule is bound and stabilized by R229.Glycerol uptake assay on human AQP7 as well as AQP3 and AQP10 demonstrated strong glycerol transportation activities at the physiological condition.The human AQP7 structure,in combination with the molecular dynamics simulation thereon,reveals a fully closed conformation with its permeation pathway strictly confined by the Ar/R filter at the exoplasmic side and the gate at the cytoplasmic side,and the binding of glycerol at the Ar/R filter plays a critical role in controlling the glycerol flux by driving the dislocation of the residues at narrowest parts of glycerol pathway in AQP7.