engleski

Histological aspects of sepsis - induced brain changes in a baboon model

Encephalophaty is one of the organ dysfunctions seen in critically ill patients with multiple organ dysfunction syndrome secondary to sepsis, but only few clinical studies are available. To gain an insight into the role of oxidative stress in the patophysiology of brain, we have performed an immunohistochemical analysis of the distribution of 4-hydroxynonenal (HNE) in the brain of 14 baboons with chronic instrumentation and fluid support for 3 days. Septic shock was induced by i.v. infusion of live E.coli (2x109 CFU/kg)over 2 hours. For the immunohistochemical detection of the HNE-adducts, immunoperoxidase technique was used on standard paraffin sections. Monoclonal antibodies from the clone "HNE Ig4" were used. The antibody is specific for the HNE-histidine epitope in HNE-protein (peptide) conjugates. Very strong immunohistochemical staining on HNE was observed for almost all animals in the subarachnoidal space and the brain white matter. On the contrary, the presence of the aldehyde was less obvious in the gray matter of the brain, and could not be even detected in some animals. Perivascular edema fluid of the brain, as well as the hemolytic content of the blood vessels were rich in HNE-protein adducts. Strong HNE positivity was noticed in the brain membranes and the blood vessels, particulary in subarachnoidal space. Swelling of the astrocytes was associated with HNE presence and much more pronounced in the midbrain than in the other brain regions. Similary, more HNE-positive neurons were found in the midbrain thai in the other parts of the brain. Due to these findings, we suppose that the brain damage induced by sepsis could be based on the oxidative damage of the blood brain barrier and the release of the "second toxic messengers of free radicals" (such as HNE) from the blood vessels into the brain.

oxidative stress, brain, sepsis, HNE, immunohistochemistry, baboon, neuropathology

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