Blood-brain barrier derangement in sepsis: cause of septic encephalopathy?
Patients with sepsis often manifest disorientation, somnolence, asterixis and coma, symptoms also seen in portasystemic encephalopathy. Altered plasma concentrations of the neutral amino acids and in creased blood-brain transport of these acids may play a role in portasystemic encephalopathy. Plasma amino acids and blood-brain barrier transport of neutral amino acids were investigated in a rat model of abdominal sepsis, cecal ligation and puncture. The blood-brain transport was studied by the technique of Oldendorf with carbon-14-amino acids 12 and 24 hours after the induction of sepsis. In similar groups of animals, isolation of brain capillaries was carried out by the technique of Hjelle and the capillaries were incubated with carbon-14-amino acids to study transport activity. Plasma and brain amino acids were deranged in a fashion similar to the derangements seen in portasystemic encephalopathy, with a decrease in plasma branched chain amino acids and an increase in most neutral amino acids in brain. The changes were most pronounced after 24 hours. The brain uptake of several neutral amino acids was increased in the septic rats, while the uptake of lysine, a basic amino acid, was normal. In the brain capillaries isolated from septic rats, tyrosine and leucine transport was also greater than in sham-operated animals. Elevated neutral amino acids may play a role in the encephalopathy encountered in septic patients similar to its role in patients with portasystemic encephalopathy, as similar mechanisms appear to be operating.
D000005:Abdomen; D000596:Amino Acids / Q000378:metabolism*; D000641:Ammonia / Q000097:blood; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D051381:Rats; D018805:Sepsis / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D012709:Serum Albumin / Q000378:metabolism
D000596:Amino Acids; D001786:Blood Glucose; D012709:Serum Albumin; D000641:Ammonia