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Bilirubin-induced neuronal injury likely reflects the adverse nature of hazardous unbound unconjugated bilirubin on plasma membranes and resultant excitotoxicity, neuroinflammation, oxidative stress, and perturbed cell cycle kinetics, including cell cycle arrest.
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Hazardous hyperbilirubinemia leading to acute bilirubin encephalopathy is increasingly recognized to adversely impact neural respiratory drive and manifest clinically as recurrent symptomatic central, mixed, and obstructive apnea events.
Bilirubin-Induced Neurotoxicity in the Preterm Neonate
Section snippets
Key points
Neuropathology of kernicterus
The neuropathology of bilirubin-induced brain damage is (i) remarkably similar across preterm and term neonates, and murine animal models; (ii) distinct from hypoxic-ischemic neonatal CNS injury; and (iii) notable in sparing the neocortex.1, 3 Classic kernicterus at postmortem in the preterm neonate is characterized by both (i) intense yellow staining of neurons in selected brainstem nuclear clusters and (ii) histopathologic evidence of neuronal damage in these stained regions. However,
Neuroimaging of kernicterus
MRI of the infant with kernicterus mirrors the distinct regional nature of bilirubin-induced neuropathology demonstrating abnormal bilateral, symmetric, high-intensity signals in the globus pallidus and subthalamic nuclei and on occasion the internal capsule and thalamus (Fig. 1).4, 5 Chronic bilateral, symmetrically increased T2-signal (or T2-FLAIR [fluid attenuated inversion recovery] signal) in the globus pallidus and subthalamic nuclei of an infant with a history of hyperbilirubinemia
Molecular and cellular mechanisms of bilirubin neurotoxicity
The complex cascades of molecular and cellular events that underlie bilirubin-induced neurotoxicity remain incompletely understood, but involve regional and cell-specific responses.8 Fig. 2 highlights the multiple reported effects of bilirubin on neurons and glia cells.8 Which of these effects constitute the “core” processes or molecular triggers that ultimately lead to bilirubin neurotoxicity is unclear.8, 9, 10, 11, 12 Nevertheless, the pathogenesis of bilirubin-induced neuronal cell injury
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2023, Jornal de PediatriaCitation Excerpt :Nearly all premature infants, less than 35 weeks of gestational age (GA), have elevated serum/plasma total bilirubin (TBILI) levels. After adjustment for gestational and postpartum age, premature infants are more likely than term (or late) infants to develop bilirubin-induced neurological dysfunction (BIND), which may lead to chronic neurological sequelae if not treated promptly or appropriately.3 Due to the delayed and insufficient colonization of the gastrointestinal flora in the early stage of neonates, there are a relative few microbiota involved in bilirubin metabolism, resulting in a decreased conversion of conjugated bilirubin to stercobilin, which is excreted through feces.
Neonatal Hyperbilirubinemia and Kernicterus
2023, Avery's Diseases of the NewbornTheoretical (DFT) study on the hydroxylation mechanism of Sn(IV)porphyrin: How does Sn(IV)porphyrin inhibit heme oxygenase catalysis function
2022, Journal of Molecular StructureCitation Excerpt :In addition to HO cyto-protective activities to defend neural cells against oxidative stress, neurotoxic effects of HO up-regulation in Alzheimer disease (AD) have been documented; supposed that these effects are attributed to Fe deposition [20,21]. In neonatal jaundice and some brain disorders, hyperbilirubinemia, bilirubin deposition in brain, resulted from the accumulation of unconjugated bilirubin, is responsible for severe neurological damage [22,23]. The neonatal hyperbilirubinemia has been treated through various therapeutic approaches, such as phototherapy (PT) and in severe cases, exchange transfusion (ET) whereby the accumulated bilirubin in body is removed [24].
Current status of neonatal jaundice management in Japan
2023, Pediatrics InternationalPerinatal Hemolytic Disorders and Identification Using End Tidal Breath Carbon Monoxide
2023, Current Pediatric Reviews
Disclosure Statement: Dr J.F. Watchko reports serving as a consultant in legal cases related to neonatal jaundice. No other potential conflict of interest relevant to this article was reported.
Support: The Mario Lemieux Foundation and The 25 Club of Magee-Womens Hospital.