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

Background: The aim of this study was to histologically investigate brain d amage after prolonged periods of bacteremia in pigs. Methods: Twenty-one pathogen-free Gottingen minipigs were anesthetized and instrumented with a femoral arterial, a pulmonary arterial, and through mid line 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 instrument ation, the animals were randomized in two groups: septic and control animal s. The septic group received an Infusion of 10(7) colony-forming units per kilogram of living Escherichia coli over 0.5 h through portal venous cathet er each day. The control group received saline. Postoperative intensive car e treatment included 4 days of controlled mechanical ventilation, sedation, and intravenous nutrition. The brains then were removed, fixed, and proces sed for histology, Each pathologic alteration found in the samples was asse ssed and given a severity code (0-3). Results: Sham-operated animals showed no alterations caused by the instrume ntation and the intensive care treatment. The septic group showed typical c linical signs of sepsis, Vasopressor support and mechanical ventilation pre vented systemic hypotension and hypoxemia, High serum and cerebrospinal flu id levels of interleukin-6 and tumor necrosis factor-alpha were detected. T he septic group showed severe histologic abnormalities of the brain includi ng perivascular edema, spongiform degeneration, hyperemia, and purpura. Dam age 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 rela ted to systemic hypoxia or ischemia. High cerebrospinal fluid levels of tum or necrosis factor-alpha and interleukin-6 were related to an inflammatory process in the brain resulting in cerebral edema and death of neurons.