Brain bilirubin deposition and brain blood flow during acute urea-induced hyperosmolality in newborn piglets

Acute hyperosmolality-induced blood brain barrier breakdown has been demonstrated to increase the permeability of sucrose, which is similar in molecular weight to bilirubin, independently of changes in regional brain blood flow. We studied three groups of piglets given continuous bilirubin infusions to maintain serum bilirubin concentrations at approximately 8 mg/dl. Normal serum osmolality was maintained throughout the study in control animals. Two experimental groups were made hyperosmolar (330 and 375 mosmol/liter) with bolus urea infusions during the last hour of the study. Regional brain bilirubin concentrations were elevated in the 375 mosmol/liter hyperosmolal experimental group, but not in the 330 mosmol/liter group. Regional brain albumin concentrations also were increased over the control group in the 375 mosmol/liter animals. There were no differences in regional brain blood flows to account for the increases in brain bilirubin concentrations. Our results show that brain bilirubin deposition occurs following breakdown of the blood brain barrier by acute, severe hyperosmolality (375 mosmol/liter) and that the deposited bilirubin is derived from both bound and unbound fractions. The bilirubin deposition occurs independently of changes in regional brain blood flow; however, regional differences in the blood brain barrier permeability to albumin also occur.