ArticleJournal of neuroinflammation2017
Inflammatory signature of cerebellar neurodegeneration during neonatal hyperbilirubinemia in Ugt1
Article in Journal of neuroinflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- The Role of ER Stress in Bilirubin Neurotoxicity: A Complex Molecular Network.Antioxidants (Basel, Switzerland) · 2026Review
- Integrated machine learning identifies biomarkers for bilirubin-induced Alzheimer's disease-like lesions in neonates and adults.Scientific reports · 2025Article
- Transcriptomic and Proteomic Changes in the Brain Along with Increasing Phenotypic Severity in a Rat Model of Neonatal Hyperbilirubinemia.International journal of molecular sciences · 2025Article
- H3K18 lactylation-mediated nucleotide-binding oligomerization domain-2 (NOD2) expression promotes bilirubin-induced pyroptosis of astrocytes.Journal of neuroinflammation · 2025Article
- Association between red blood cell distribution width coefficient of variation and post-treatment bilirubin decline velocity in neonatal hyperbilirubinemia.Frontiers in pediatrics · 2025Article
- Reduced murine double minute-2 methylation from peripheral blood mononuclear cells correlates with enhanced oxidative stress in hepatitis b virus-related hepatocellular carcinoma.Frontiers in microbiology · 2025Article
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- Strontium Attenuates Hippocampal Damage via Suppressing Neuroinflammation in High-Fat Diet-Induced NAFLD Mice.International journal of molecular sciences · 2023Article
- Bilirubin-Induced Neurological Damage: Current and Emerging iPSC-Derived Brain Organoid Models.Cells · 2022Review
- Vascular network expansion, integrity of blood-brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat.Fluids and barriers of the CNS · 2022Article
- Predictive value of different bilirubin subtypes for clinical outcomes in patients with acute ischemic stroke receiving thrombolysis therapy.CNS neuroscience & therapeutics · 2022Article
- Diagnostic methods for neonatal hyperbilirubinemia: benefits, limitations, requirements, and novel developments.Pediatric research · 2021Review
- Pathological Significance and Prognostic Roles of Indirect Bilirubin/Albumin Ratio in Hepatic Encephalopathy.Frontiers in medicine · 2021Article
- Novel Neuroprotective Potential of Crocin in Neurodegenerative Disorders: An Illustrated Mechanistic Review.Neurochemical research · 2020Review
- The Role of Bilirubin and the Other "Yellow Players" in Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Quantitative proteomic characterization of microvesicles/exosomes from the cerebrospinal fluid of patients with acute bilirubin encephalopathy.Molecular medicine reports · 2020Article
- Minocycline protects neurons against glial cells-mediated bilirubin neurotoxicity.Brain research bulletin · 2020Article
- Experimental models assessing bilirubin neurotoxicity.Pediatric research · 2020Review
- A Fragment of Apolipoprotein E4 Leads to the Downregulation of a CXorf56 Homologue, a Novel ER-Associated Protein, and Activation of BV2 Microglial Cells.Oxidative medicine and cellular longevity · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSevere hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced neurological damage and eventually death by kernicterus. Bilirubin neurotoxicity is characterized by a wide array of neurological deficits, including irreversible abnormalities in motor, sensitive and cognitive functions, due to bilirubin accumulation in the brain. Despite the abundant literature documenting the in vitro and in vivo toxic effects of bilirubin, it is unclear which molecular and cellular events actually characterize bilirubin-induced neurodegeneration in vivo.
methodsWe used a mouse model of neonatal hyperbilirubinemia to temporally and spatially define the response of the developing cerebellum to the bilirubin insult.
resultsWe showed that the exposure of developing cerebellum to sustained bilirubin levels induces the activation of oxidative stress, ER stress and inflammatory markers at the early stages of the disease onset. In particular, we identified TNFα and NFKβ as key mediators of bilirubin-induced inflammatory response. Moreover, we reported that M1 type microglia is increasingly activated during disease progression. Failure to counteract this overwhelming stress condition resulted in the induction of the apoptotic pathway and the generation of the glial scar. Finally, bilirubin induced the autophagy pathway in the stages preceding death of the animals.
conclusionsThis study demonstrates that inflammation is a key contributor to bilirubin damage that cooperates with ER stress in the onset of neurotoxicity. Pharmacological modulation of the inflammatory pathway may be a potential intervention target to ameliorate neonatal lethality in Ugt1
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