title: Effects of lipopolysaccharide infusion on arterial levels and transcerebral exchange kinetics of glutamate and glycine in healthy humans.
abstract: An imbalance between glutamate and glycine signalling may contribute to sepsis-associated encephalopathy by causing neuronal excitotoxicity. In this study, we therefore investigated the transcerebral exchange kinetics of glutamate and glycine in a human-experimental model of systemic inflammation. Cerebral blood flow (CBF) and arterial to jugular venous concentration differences of glutamate and glycine were determined before and after a 4-h intravenous infusion of Escherichia coli lipopolysaccharide (LPS, total dose of 0.3 ng/kg) in 12 healthy volunteers. The global cerebral net exchange was calculated by multiplying CBF with the arterial to jugular venous differences. LPS induced a systemic inflammatory response with fever, neutrocytosis, and elevated arterial levels of tumour necrosis factor-α. This was associated with a decrease in the arterial levels of both glutamate and glycine; however, their transcerebral exchange kinetics were unaffected. Inflammation-induced alterations of the circulating levels of glutamate and glycine, do not affect the global transcerebral exchange kinetics of these amino acids in healthy humans.
authors.affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, University Hospital Rigshospitalet, Copenhagen, Denmark. ronan@dadlnet.dk
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.forename: Sarah
authors.initials: S
authors.lastname: Taudorf
authors.forename: Damian M
authors.initials: DM
authors.lastname: Bailey
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
authors.forename: Fin S
authors.initials: FS
authors.lastname: Larsen
authors.forename: Bente K
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D018698:Glutamic Acid / Q000097:blood / Q000378:metabolism*; D005998:Glycine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D018805:Sepsis / Q000097:blood / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid; D005998:Glycine