The effects of brain blood flow on brain bilirubin deposition in newborn piglets
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Increased brain blood flow during hypercapnia may lead to greater bilirubin deposition in infant brains. This finding suggests a potential link between blood flow, bilirubin levels, and kernicterus risk in vulnerable newborns.
Area of Science:
- Neonatal Neurology
- Neuroscience
- Bilirubin Metabolism
Background:
- Kernicteric lesions typically affect subcortical brain regions.
- These areas experience high blood flow during asphyxia and hypercapnia.
Purpose of the Study:
- To investigate the hypothesis that increased brain bilirubin deposition correlates with elevated brain blood flow.
- To examine the impact of hypercapnia on regional brain blood flow and bilirubin deposition in piglets.
Main Methods:
- Piglets received bilirubin infusions to achieve target serum levels.
- Regional brain blood flow and bilirubin content were measured.
- Hypercapnia was induced in a subset of piglets (PaCO2 ~70 mm Hg).
- Albumin infusion was used to assess blood-brain barrier integrity.
Main Results:
- Hypercapnia significantly increased regional brain blood flow and bilirubin deposition in subcortical areas, midbrain, and cerebellum.
- Hypercapnia did not increase regional brain albumin content, indicating intact blood-brain barrier.
- A positive correlation was observed between augmented brain blood flow and bilirubin deposition.
Conclusions:
- Hypercapnia-induced increases in regional brain blood flow are associated with enhanced deposition of unbound bilirubin.
- The findings suggest a potential mechanism linking brain blood flow and bilirubin neurotoxicity.
- Further research is needed to establish causality and the role in kernicterus development.
Abstract:
Since kernicteric lesions are usually found in the subcortical regions of the brain and these areas also receive the highest blood flow during asphyxia and hypercapnia, we hypothesized that increases in brain bilirubin deposition may be related to increases in brain blood flow. Fourteen piglets underwent a 3-h infusion of bilirubin to maintain total serum bilirubin at approximately 8 mg/dl, during which time blood gases, hemodynamic variables, and brain blood flow were determined. After sacrificing the animals, regional brain bilirubin content was determined. Ten piglets underwent the same protocol; in addition, hypercapnia was induced during the last hour of study (PaCO2 approximately 70 mm Hg). The regional brain blood flow and bilirubin deposition were significantly increased over control values (p less than 0.05) following hypercapnia in the subcortical region and significantly so in the midbrain and cerebellum. In separate groups of control (n = 6) and hypercapnia (n = 6) piglets, 125I-labeled albumin was infused and demonstrated that hypercapnia was not associated with increased regional brain albumin content. We conclude that hypercapnia-induced augmentation in regional brain blood flow is associated with increased deposition brain blood flow is associated with increased deposition of unbound bilirubin. Although the causal relationship between these two observations has not been firmly established, the findings deserve future investigation to clarify the role of brain blood flow, brain bilirubin deposition, and the production of kernicterus in high risk infants.