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

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.