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

Berg RM, Taudorf S, Bailey DM, Lundby C, Larsen FS, Pedersen BK, Møller K - Crit Care (2010)

Bottom Line: 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.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.Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ronan@dadlnet.dk

ABSTRACT

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.

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Related in: MedlinePlus

Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
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Figure 2: Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.

Mentions: LPS infusion increased plasma phenylalanine and decreased the concentration of all other LNAAs except isoleucine (Table 1), with a concurrent reduction in the BCAA/AAA ratio (baseline, 5.2 (4.7-5.7); LPS, 4.9 (4.4-5.3); Figure 1). Both the cerebral delivery (Table 2) and the unidirectional cerebral influx of phenylalanine increased (baseline, 8.3 (6.7-9.9) nmol/g/min; LPS, 9.2 (8.9-10.4) nmol/g/min; Figure 2), whereas its cerebral net exchange was unchanged (Table 3). Furthermore, a net cerebral influx observed at baseline for leucine and isoleucine was abolished after LPS infusion (Table 3). At baseline, a net cerebral influx of methionine was present; this was converted to a net cerebral efflux after LPS infusion (Table 3). Furthermore, a net cerebral efflux of glutamine that was not observed at baseline was present after LPS infusion (Table 3). There was no effect of LPS infusion on the arterial whole-blood concentration of ammonia (baseline, 78 (72-84] μmol/L; LPS, 69 (61-76) μmol/L; NS). The cerebral net exchange of ammonia did not differ from 0 at any time and was unaffected by LPS infusion (baseline, 139 ([-70] - 348) nmol/100 g/min; LPS, -98 ([-618] - 422) nmol/100 g/min; NS).


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

Berg RM, Taudorf S, Bailey DM, Lundby C, Larsen FS, Pedersen BK, Møller K - Crit Care (2010)

Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875531&req=5

Figure 2: Unidirectional cerebral influx of phenylalanine (Jin, Phe) after lipopolysaccharide (LPS) infusion in healthy humans. Triangles indicate means. **Different from baseline, P < 0.01.
Mentions: LPS infusion increased plasma phenylalanine and decreased the concentration of all other LNAAs except isoleucine (Table 1), with a concurrent reduction in the BCAA/AAA ratio (baseline, 5.2 (4.7-5.7); LPS, 4.9 (4.4-5.3); Figure 1). Both the cerebral delivery (Table 2) and the unidirectional cerebral influx of phenylalanine increased (baseline, 8.3 (6.7-9.9) nmol/g/min; LPS, 9.2 (8.9-10.4) nmol/g/min; Figure 2), whereas its cerebral net exchange was unchanged (Table 3). Furthermore, a net cerebral influx observed at baseline for leucine and isoleucine was abolished after LPS infusion (Table 3). At baseline, a net cerebral influx of methionine was present; this was converted to a net cerebral efflux after LPS infusion (Table 3). Furthermore, a net cerebral efflux of glutamine that was not observed at baseline was present after LPS infusion (Table 3). There was no effect of LPS infusion on the arterial whole-blood concentration of ammonia (baseline, 78 (72-84] μmol/L; LPS, 69 (61-76) μmol/L; NS). The cerebral net exchange of ammonia did not differ from 0 at any time and was unaffected by LPS infusion (baseline, 139 ([-70] - 348) nmol/100 g/min; LPS, -98 ([-618] - 422) nmol/100 g/min; NS).

Bottom Line: 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.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.Systemic inflammation may affect brain function by reducing the BCAA/AAA ratio, thereby changing the cerebral net exchange of LNAAs.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centre of Inflammation and Metabolism, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. ronan@dadlnet.dk

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus