Cerebral net exchange of large neutral amino acids after lipopolysaccharide infusion in healthy humans.
BACKGROUND
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.
Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ronan@dadlnet.dk
Ronan Mg
RM
Berg
Sarah
S
Taudorf
Damian M
DM
Bailey
Carsten
C
Lundby
Fin Stolze
FS
Larsen
Bente Klarlund
BK
Pedersen
Kirsten
K
Møller
D000328:Adult; D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000641:Ammonia / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000596:Amino Acids; D015415:Biomarkers; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000641:Ammonia