A reassessment of the blood–brain barrier transport of large neutral amino acids during acute systemic inflammation in humans

TY - JOUR

T1 - A reassessment of the blood–brain barrier transport of large neutral amino acids during acute systemic inflammation in humans

AU - Dahl, Rasmus H.

AU - Berg, Ronan M.G.

AU - Taudorf, Sarah

AU - Bailey, Damian M.

AU - Lundby, Carsten

AU - Larsen, Fin S.

AU - Møller, Kirsten

PY - 2018

Y1 - 2018

N2 - We reassessed data from a previous study on the transcerebral net exchange of large neutral amino acids (LNAAs) using a novel mathematical model of blood–brain barrier (BBB) transport. The study included twelve healthy volunteers who received a 4-h intravenous lipopolysaccharide (LPS) infusion (total dose: 0·3 ng/kg), a human experimental model of the systemic inflammatory response during the early stages of sepsis. Cerebral blood flow and arterial-to-jugular venous LNAA concentrations were measured prior to and after LPS, and the BBB transport and brain extracellular concentrations of LNAAs were calculated. The arterial concentration and unidirectional cerebral influx of phenylalanine increased after LPS. The BBB transport of tyrosine was unaffected, while its concentration in the brain extracellular fluid increased. These findings suggest that LPS infusion leads to an increased cerebral uptake of phenylalanine, which is then metabolized to tyrosine. This may reflect a neuroprotective mechanism that ‘detoxifies’ excess intracerebral phenylalanine in the clinical setting of sepsis.

AB - We reassessed data from a previous study on the transcerebral net exchange of large neutral amino acids (LNAAs) using a novel mathematical model of blood–brain barrier (BBB) transport. The study included twelve healthy volunteers who received a 4-h intravenous lipopolysaccharide (LPS) infusion (total dose: 0·3 ng/kg), a human experimental model of the systemic inflammatory response during the early stages of sepsis. Cerebral blood flow and arterial-to-jugular venous LNAA concentrations were measured prior to and after LPS, and the BBB transport and brain extracellular concentrations of LNAAs were calculated. The arterial concentration and unidirectional cerebral influx of phenylalanine increased after LPS. The BBB transport of tyrosine was unaffected, while its concentration in the brain extracellular fluid increased. These findings suggest that LPS infusion leads to an increased cerebral uptake of phenylalanine, which is then metabolized to tyrosine. This may reflect a neuroprotective mechanism that ‘detoxifies’ excess intracerebral phenylalanine in the clinical setting of sepsis.

KW - aromatic amino acids

KW - endotoxaemia

KW - false neurotransmitters

KW - sepsis

KW - sepsis-associated encephalopathy

U2 - 10.1111/cpf.12463

DO - 10.1111/cpf.12463

M3 - Journal article

C2 - 28795486

AN - SCOPUS:85048472437

SN - 1475-0961

VL - 38

SP - 656

EP - 662

JO - Clinical Physiology and Functional Imaging

JF - Clinical Physiology and Functional Imaging

IS - 4

ER -