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Background: The pathophysiology of neurocognitive dysfunction and developmental delay after cardiopulmonary bypass (CPB) in infants is not known. It is known that head trauma, stroke, and seizures cause dysfunction of the blood brain barrier (BBB) that is associated with increased inducible transcription factor gene expression in the cells of the barrier. The purpose of this study was to determine the effects of CPB and hypothermic circulatory arrest on expression of the transcription factor FOS and the function of the BBB in an infant animal model.Methods: Infant lambs (n = 36; 10–12 days) were exposed to 0, 15, 30, 60, or 120 minutes of normothermic (38°C) CPB or 2 hours of hypothermic circulatory arrest at 16°C. After terminating bypass 15 animals had their brains perfusion-fixed and removed for immunohistochemical analysis of expression of the transcription factor FOS. The other animals were perfused with fluorescent albumin to visualize the brain microvasculature. Brain sections were analyzed with a laser scanning confocal microscope.Results: Control animals (n = 6, sham operated and cannulated) exhibited normal vasculature with negligible leakage and no FOS protein expression in neurons or endothelial cells anywhere in the brain. Significant FOS expression in barrier-associated structures including the blood vessels, choroid plexus, and ependyma but not neurons occurred at all times on bypass. CPB caused leakage of fluorescent albumin from blood vessels in all animals. Two hours of normothermic CPB (n = 4) caused significant (p < 0.01) leakage in the cerebellum, cortex, hippocampus, and corpus callosum. Animals exposed to circulatory arrest experienced severe leakage throughout the brain (p < 0.001) and FOS expression in all cells.Conclusions: These experiments indicate that the BBB is dysfunctional after all time points on normothermic CPB, BBB dysfunction is worsened by hypothermic circulatory arrest, and BBB dysfunction is associated with intense molecular activity within the barrier-forming cells. Dysfunction of the BBB may contribute to neurologic complications after heart surgery. [Copyright &y& Elsevier]

Neurological diseases are often associated with cerebrovascular dysfunction and changes in blood–brain barrier (BBB) function. This is important for two seemingly conflicting reasons. On the one hand, a leaky BBB may lead to brain disease by allowing extravasation of cells and molecules normally segregated in the periphery, while on the other hand an intact BBB may hamper drug delivery to the ailing brain. Under both circumstances, it would be desirable to follow closely over time BBB “tightness”. Several lines of evidence have suggested that the astrocytic protein S100β is a potentially useful peripheral marker of BBB permeability. Other markers of brain-to-blood barriers have been recently discovered by a proteomic approach. These proteins are virtually absent in normal blood, appear in serum from patients with cerebral lesions, and can be easily detected. We will present clinical and laboratory evidence supporting the use of these markers as modern neurodiagnostic tools. [Copyright &y& Elsevier]