Cerebral histopathology following portal venous infusion of bacteria in a chronic porcine model

Anesthesiology. 2000 Sep;93(3):793-804. doi: 10.1097/00000542-200009000-00029.


Background: The aim of this study was to histologically investigate brain damage after prolonged periods of bacteremia in pigs.

Methods: Twenty-one pathogen-free Göttingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through midline abdominal incision with a portal venous catheter. After craniotomy the superior sagittal sinus was cannulated. A lumbosacral spinal catheter was inserted for sampling of cerebrospinal fluid. Twelve hours after instrumentation, the animals were randomized in two groups: septic and control animals. The septic group received an infusion of 107 colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous catheter each day. The control group received saline. Postoperative intensive care treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and processed for histology. Each pathologic alteration found in the samples was assessed and given a severity code (0-3).

Results: Sham-operated animals showed no alterations caused by the instrumentation and the intensive care treatment. The septic group showed typical clinical signs of sepsis. Vasopressor support and mechanical ventilation prevented systemic hypotension and hypoxemia. High serum and cerebrospinal fluid levels of interleukin-6 and tumor necrosis factor-alpha were detected. The septic group showed severe histologic abnormalities of the brain including perivascular edema, spongiform degeneration, hyperemia, and purpura. Damage of neurons was seen including eosinophilic cytoplasm, shrunken nuclei, and disintegration of the nuclear membrane.

Conclusions: Abdominal sepsis induced severe brain damage that was not related to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tumor necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteremia / metabolism
  • Bacteremia / pathology*
  • Body Temperature
  • Brain / metabolism
  • Brain / pathology*
  • Brain Edema / etiology
  • Chronic Disease
  • Female
  • Interleukin-6 / biosynthesis
  • Portal Vein
  • Swine
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Interleukin-6
  • Tumor Necrosis Factor-alpha