Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans

TY - JOUR

T1 - Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans

AU - Berg, Ronan Mg

AU - Taudorf, Sarah

AU - Bailey, Damian M

AU - Lundby, Carsten

AU - Larsen, Fin Stolze

AU - Pedersen, Bente Klarlund

AU - Møller, Kirsten

AU - Møller, Kirsten

PY - 2010/2/11

Y1 - 2010/2/11

N2 - Introduction: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.Methods: The BCAA/AAA ratio, the cerebral delivery, and net exchange of LNAAs and ammonia were measured before and 1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) in 12 healthy young men.Results: LPS induced systemic inflammation, reduced the BCAA/AAA ratio, increased the cerebral delivery and unidirectional influx of phenylalanine, and abolished the net cerebral influx of the BCAAs leucine and isoleucine. Furthermore, a net cerebral efflux of glutamine, which was independent of the cerebral net exchange of ammonia, was present after LPS infusion.Conclusions: Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

AB - Introduction: Alterations in circulating large neutral amino acids (LNAAs), leading to a decrease in the plasma ratio between branched-chain and aromatic amino acids (BCAA/AAA ratio), may be involved in sepsis-associated encephalopathy. We hypothesised that a decrease in the BCAA/AAA ratio occurs along with a net cerebral influx of the neurotoxic AAA phenylalanine in a human experimental model of systemic inflammation.Methods: The BCAA/AAA ratio, the cerebral delivery, and net exchange of LNAAs and ammonia were measured before and 1 hour after a 4-hour intravenous infusion of Escherichia coli lipopolysaccharide (LPS) in 12 healthy young men.Results: LPS induced systemic inflammation, reduced the BCAA/AAA ratio, increased the cerebral delivery and unidirectional influx of phenylalanine, and abolished the net cerebral influx of the BCAAs leucine and isoleucine. Furthermore, a net cerebral efflux of glutamine, which was independent of the cerebral net exchange of ammonia, was present after LPS infusion.Conclusions: Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

U2 - 10.1186/cc8873

DO - 10.1186/cc8873

M3 - Journal article

SN - 1466-609X

VL - 14

SP - R16

JO - Critical Care (Online Edition)

JF - Critical Care (Online Edition)

IS - 1

ER -