S-100 Protein and Neurohistopathologic Changes in a Porcine Model of Acute Lung Injury

Background: Survivors of acute respiratory distress syndrome exhibit neuropsychological sequelae that might be attributable to hippocampal damage. The authors sought to determine the effects of hypoxemia in a pig model of acute lung injury on the hippocampal region and the release of S-100 protein in comparison to a control group in which hypoxemia was induced by reducing the inspired oxygen fraction. Methods: Hypoxemia was induced in 14 female pigs by repeated lung lavages (lung injury group; n = 7) or by reducing the inspired oxygen fraction (hypoxia-only group; n = 7). Hemodynamic variables, gas exchange, and serum concentrations of S-100 protein were measured at baseline, after induction of acute lung injury, and subsequently for 12 h. Animals were euthanized, and the brains were removed for histopathologic examination. Results: Comparable blood gases were seen in both groups. Serum S-100 protein concentrations were comparable for both groups at baseline. At all other time points, S-100 concentrations were significantly higher in the lung injury group. Neuropathologic examination showed basophilic and shrunken neurons of the pyramidal cell layer in the hippocampal CA1 subregion of all pigs in the lung injury group. Few abnormalities were seen in the hypoxia-only group. Conclusions: The same degree of hypoxemia induced in a lavage model of acute lung injury results in greater brain damage assessed by S-100 protein and histopathologic findings when compared to a group in which hypoxemia at the same degree was induced by reducing the inspired oxygen fraction. This suggests that acute lung injury leads to neuropathologic changes independent of hypoxemia.

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