The in Vivo Effect of Bilirubin and Sulfisoxazole on Cerebral Oxygen, Glucose, and Lactate Metabolism in Newborn Piglets

Brann, Benjamin S; Stonestreet, Barbara S.; Oh, William; Cashore, William J.

doi:10.1203/00006450-198708000-00006

Cited by 20 publications

(7 citation statements)

References 19 publications

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“…In contrast to the results of previous studies [9,26,33], significant reduction in mean arterial pressure and metabolic acidosis were observed in both BG and NG. Since a similar amount of bilirubin was given, and comparable brain bilirubin levels was achieved, the reasons for this discrepancy are difficult to explain.…”

Section: Discussioncontrasting

confidence: 56%

“…Decreased blood-to-brain glucose ratio and increased lactate level in the blood and brain observed in BG also indicate secondarily increased anaerobic glycolysis to compensate for the bilirubin-induced mitochon-Park/Chang/Lee drial damage and energy depletion. However, similar experiments done in guinea pig [31], Gunn rat [32] and newborn piglet [33] failed to document a marked change in cerebral glucose metabolism or oxidative phosphorylation. These discrepancies might be attributable to differences in animal species, bilirubin dosage and duration of exposure.…”

Section: Discussionmentioning

confidence: 90%

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Effect of 7-Nitroindazole on Bilirubin-Induced Changes in Brain Cell Membrane Function and Energy Metabolism in Newborn Piglets

Park

Chang

Lee³

2002

Neonatology

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We evaluated the effects of 7-nitroindazole, a selective neuronal nitric oxide synthetase (nNOS) inhibitor, on bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglets. The decreased cerebral cortical cell membrane Na⁺,K⁺-ATPase activity and increased lipid peroxidation products, indicative of bilirubin-induced brain damage, were significantly attenuated by 7-nitroindazole treatment. 7-Nitroindazole also significantly improved the bilirubin-induced reduction in both brain ATP and phosphocreatine levels, decreased blood-to-brain glucose ratio and increased brain lactate level. In summary, 7-nitroindazole significantly attenuated the bilirubin-induced alterations in brain cell membrane function and energy metabolism in the newborn piglet. These findings suggest that nitric oxide produced by nNOS is involved in mediating or facilitating bilirubin-induced cerebral dysfunction.

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 90%

Effect of 7-Nitroindazole on Bilirubin-Induced Changes in Brain Cell Membrane Function and Energy Metabolism in Newborn Piglets

Park

Chang

Lee³

2002

Neonatology

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“…Indeed, in order to be clinically relevant, we induced a moderate (150–250 μmol/L) and sustained (17 h) HB in a (late) preterm animal. In contrast, previous studies reported data from more severe (from 220 to 1300 μmoles/L) and shorter duration HB (ranging from one injection to 4 h infusion) (Ahlfors et al, 1986 ; Brann et al, 1987 ; Park et al, 2001 ; Mesner et al, 2008 ; Ye et al, 2012 ). To our knowledge, there has been only one previous study on “moderate” HB (100–200 μmoles/L), but with considerably shorter HB duration (2 h) (Roger et al, 1995 ).…”

Section: Discussionmentioning

confidence: 91%

“…Compared to previous animal models of neonatal HB (Ahlfors et al, 1986 ; Brann et al, 1987 ; Park et al, 2001 ; Mesner et al, 2008 ; Ye et al, 2012 ), our preterm ovine model of moderate HB has several unique features. Indeed, in order to be clinically relevant, we induced a moderate (150–250 μmol/L) and sustained (17 h) HB in a (late) preterm animal.…”

Section: Discussionmentioning

confidence: 94%

Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

et al. 2016

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Hyperbilirubinemia (HB) occurs in 90% of preterm newborns. Moderate HB can induce acute neurological disorders while severe HB has been linked to a higher incidence of apneas of prematurity. The present study aimed to test the hypothesis that even moderate HB disrupts cardiorespiratory control in preterm lambs. Two groups of preterm lambs (born 14 days prior to term), namely control (n = 6) and HB (n = 5), were studied. At day 5 of life, moderate HB (150–250 μmol/L) was induced during 17 h in the HB group after which cardiorespiratory control as well as laryngeal and pulmonary chemoreflexes were assessed during baseline recordings and during hypoxia. Recordings were repeated 72 h after HB induction, just before euthanasia. In addition, neuropathological studies were performed to investigate for cerebral bilirubin deposition as well as for signs of glial reactivity in brainstem structures involved in cardiorespiratory control. Results revealed that sustained and moderate HB: (i) decreased baseline respiratory rate and increased the time spent in apnea; (ii) blunted the cardiorespiratory inhibition normally observed during both laryngeal and pulmonary chemoreflexes; and (iii) increased heart rate in response to acute hypoxia. These acute physiological changes were concurrent with an activation of Alzheimer type II astrocytes throughout the brain, including the brainstem. Concomitantly, bilirubin deposits were observed in the leptomeninges, but not in brain parenchyma. While most cardiorespiratory alterations returned to normal 72 h after HB normalization, the expression of glial fibrillary acid protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) was still increased within the nucleus tractus solitarius. In conclusion, moderate and sustained HB in preterm lambs induced cardiorespiratory alterations, the latter of which were associated with neurohistopathological changes. These changes are indicative of an inflammatory response in the brainstem neuroanatomical substrates involved in cardiorespiratory control.

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“…Animals such as rat (7), piglet (8), and rhesus monkey (9) show the increased bilirubin deposition in brain upon drug administration. Extrapolation of results of these studies using an animal model to humans is only useful when the test animal albumin binds bilirubin as well as the drug in the same manner as the human albumin binds.…”

mentioning

confidence: 99%

Comparison of bilirubin binding and other molecular properties of tile serum albumin of several mammalian species

1998

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SUMMARYIn order to develop an animal model for /n vivo testing of the displacing action of various drugs and for study of the bilirubin deposition in the brain, some molecular properties of the serum albumin from different species i.e. pig, cat, human, dog, sheep, guinea pig and rat were investigated. These albumins were found to have differences in molecular weight, Stokes radius and electrophoretic mobility. They also showed different bilirubin binding characteristics when studied by spectroscopy and fluorescence quenching. It is therefore, necessary to consider the species differences when results of animal experimentation are used as a basis for the investigation of human kernicterus.

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The in Vivo Effect of Bilirubin and Sulfisoxazole on Cerebral Oxygen, Glucose, and Lactate Metabolism in Newborn Piglets

Cited by 20 publications

References 19 publications

Effect of 7-Nitroindazole on Bilirubin-Induced Changes in Brain Cell Membrane Function and Energy Metabolism in Newborn Piglets

Effect of 7-Nitroindazole on Bilirubin-Induced Changes in Brain Cell Membrane Function and Energy Metabolism in Newborn Piglets

Moderate Hyperbilirubinemia Alters Neonatal Cardiorespiratory Control and Induces Inflammation in the Nucleus Tractus Solitarius

Comparison of bilirubin binding and other molecular properties of tile serum albumin of several mammalian species

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