Molecular events in brain bilirubin toxicity revisited.
Journal
Pediatric research
ISSN: 1530-0447
Titre abrégé: Pediatr Res
Pays: United States
ID NLM: 0100714
Informations de publication
Date de publication:
20 Feb 2024
20 Feb 2024
Historique:
received:
21
12
2023
accepted:
28
01
2024
revised:
17
01
2024
medline:
21
2
2024
pubmed:
21
2
2024
entrez:
20
2
2024
Statut:
aheadofprint
Résumé
The mechanisms involved in bilirubin neurotoxicity are still far from being fully elucidated. Several different events concur to damage mainly the neurons among which inflammation and alteration of the redox state play a major role. An imbalance of cellular calcium homeostasis has been recently described to be associated with toxic concentrations of bilirubin, and this disequilibrium may in turn elicit an inflammatory reaction. The different and age-dependent sensitivity to bilirubin damage must also be considered in describing the dramatic clinical picture of bilirubin-induced neurological damage (BIND) formerly known as kernicterus spectrum disorder (KSD). This review aims to critically address what is known and what is not in the molecular events of bilirubin neurotoxicity to provide hints for a better diagnosis and more successful treatments. Part of these concepts have been presented at the 38th Annual Audrey K. Brown Kernicterus Symposium of Pediatric American Society, Washington DC, May 1, 2023.
Identifiants
pubmed: 38378754
doi: 10.1038/s41390-024-03084-9
pii: 10.1038/s41390-024-03084-9
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.
Références
Jayanti, S., Ghersi-Egea, J.-F., Strazielle, N., Tiribelli, C. & Gazzin, S. Severe neonatal hyperbilirubinemia and the brain: the old but still evolving story. Pediatr. Med. 4, 4–37 (2021).
Gazzin, S. et al. Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups. Pediatr. Res. 71, 653–660 (2012).
pubmed: 22337225
doi: 10.1038/pr.2012.23
Gazzin, S., Jayanti, S. & Tiribelli, C. Models of bilirubin neurological damage: lessons learned and new challenges. Pediatr. Res. 93, 1838–1845 (2023).
Diamond, I. & Schmid, R. Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system. J. Clin. Invest. 45, 678–689 (1966).
pubmed: 5949114
pmcid: 292745
doi: 10.1172/JCI105383
Sawasaki, Y., Yamada, N. & Nakajima, H. Developmental features of cerebellar hypoplasia and brain bilirubin levels in a mutant (Gunn) rat with hereditary hyperbilirubinaemia. J. Neurochem. 27, 577–583 (1976).
pubmed: 966000
doi: 10.1111/j.1471-4159.1976.tb12285.x
Barateiro, A. et al. Reduced myelination and increased glia reactivity resulting from severe neonatal hyperbilirubinemia. Mol. Pharmacol. 89, 84–93 (2016).
pubmed: 26480925
pmcid: 4702100
doi: 10.1124/mol.115.098228
Hansen, T. W. R. Bilirubin entry into and clearance from rat brain during hypercarbia and hyperosmolality. Pediatr. Res. 39, 72–76 (1996).
pubmed: 8825388
doi: 10.1203/00006450-199601000-00010
Hansen, T. W. R., Øyasœter, S., Stiris, T. & Bratlid, D. Effects of sulfisoxazole, hypercarbia, and hyperosmolality on entry of bilirubin and albumin into brain regions in young rats. NEO 56, 22–30 (1989).
Hansen, T. W. R. Pioneers in the scientific study of neonatal jaundice and kernicterus. Pediatrics 106, e15 (2000).
pubmed: 10920171
doi: 10.1542/peds.106.2.e15
Hansen, T. W. R. Bilirubin brain toxicity. J. Perinatol. 21, S48–S51 (2001).
pubmed: 11803417
doi: 10.1038/sj.jp.7210634
Dal Ben, M., Bottin, C., Zanconati, F., Tiribelli, C. & Gazzin, S. Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment. Sci. Rep. 7, 41032 (2017).
pubmed: 28102362
pmcid: 5244479
doi: 10.1038/srep41032
Conlee, J. W. & Shapiro, S. M. Development of cerebellar hypoplasia in jaundiced Gunn rats: a quantitative light microscopic analysis. Acta Neuropathol. 93, 450–460 (1997).
pubmed: 9144583
doi: 10.1007/s004010050639
Vianello, E. et al. Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat. Sci. Rep. 8, 13690 (2018).
pubmed: 30209300
pmcid: 6135864
doi: 10.1038/s41598-018-32106-w
Bortolussi, G. et al. Rescue of bilirubin-induced neonatal lethality in a mouse model of Crigler-Najjar syndrome type I by AAV9-mediated gene transfer. FASEB J. 26, 1052–1063 (2012).
pubmed: 22094718
pmcid: 3370676
doi: 10.1096/fj.11-195461
Nguyen, N. et al. Disruption of the Ugt1 locus in mice resembles human crigler-najjar Type I disease*. J. Biol. Chem. 283, 7901–7911 (2008).
pubmed: 18180294
doi: 10.1074/jbc.M709244200
Hu, W. et al. Ex vivo 1H nuclear magnetic resonance spectroscopy reveals systematic alterations in cerebral metabolites as the key pathogenetic mechanism of bilirubin encephalopathy. Mol. Brain 7, 87 (2014).
pubmed: 25424547
pmcid: 4252999
doi: 10.1186/s13041-014-0087-5
Roger, C., Koziel, V., Vert, P. & Nehlig, A. Effects of bilirubin infusion on local cerebral glucose utilization in the immature rat. Develop. Brain Res. 76, 115–130 (1993).
doi: 10.1016/0165-3806(93)90129-X
Roger, C., Koziel, V., Vert, P. & Nehlig, A. Regional cerebral metabolic consequences of bilirubin in rat depend upon post-gestational age at the time of hyperbilirubinemia. Develop. Brain Res. 87, 194–202 (1995).
doi: 10.1016/0165-3806(95)00076-P
Keino, H. et al. Mode of prevention by phototherapy of cerebellar hypoplasia in a new Sprague-Dawley strain of jaundiced gunn rats. PNE 12, 145–150 (1985).
Bortolussi, G. et al. Age-dependent pattern of cerebellar susceptibility to bilirubin neurotoxicity in vivo in mice. Dis. Models Mech. 7, 1057–1068 (2014).
Chang, F.-Y., Lee, C.-C., Huang, C.-C. & Hsu, K.-S. Unconjugated bilirubin exposure impairs hippocampal long-term synaptic plasticity. PLoS One 4, e5876 (2009).
pubmed: 19517010
pmcid: 2690688
doi: 10.1371/journal.pone.0005876
Robert, M. C. et al. Alterations in the cell cycle in the cerebellum of hyperbilirubinemic gunn rat: a possible link with apoptosis? PLoS One 8, e79073 (2013).
Mancuso, C. et al. Bilirubin as an endogenous modulator of neurotrophin redox signaling. J. Neurosci. Res. 86, 2235–2249 (2008).
pubmed: 18338802
doi: 10.1002/jnr.21665
Falcão, A. S. et al. Apoptosis and impairment of neurite network by short exposure of immature rat cortical neurons to unconjugated bilirubin increase with cell differentiation and are additionally enhanced by an inflammatory stimulus. J. Neurosci. Res. 85, 1229–1239 (2007).
pubmed: 17342778
doi: 10.1002/jnr.21227
Llido, J. P. et al. Bilirubin-Induced transcriptomic imprinting in neonatal hyperbilirubinemia. Biology 12, 834 (2023).
pubmed: 37372119
pmcid: 10295065
doi: 10.3390/biology12060834
Bianco, A. et al. The extent of intracellular accumulation of bilirubin determines its anti- or pro-oxidant effect. Int. J. Mol. Sci. 21, 8101 (2020).
pubmed: 33143041
pmcid: 7663266
doi: 10.3390/ijms21218101
Brito, M. A. et al. Bilirubin injury to neurons: contribution of oxidative stress and rescue by glycoursodeoxycholic acid. Neurotoxicology 29, 259–269 (2008).
pubmed: 18164405
doi: 10.1016/j.neuro.2007.11.002
Silva, R. F., Rodrigues, C. M. & Brites, D. Bilirubin-induced apoptosis in cultured rat neural cells is aggravated by chenodeoxycholic acid but prevented by ursodeoxycholic acid. J. Hepatol. 34, 402–408 (2001).
pubmed: 11322201
doi: 10.1016/S0168-8278(01)00015-0
Oakes, G. H. & Bend, J. R. Early steps in bilirubin-mediated apoptosis in murine hepatoma (Hepa 1c1c7) cells are characterized by aryl hydrocarbon receptor-independent oxidative stress and activation of the mitochondrial pathway. J. Biochem. Mol. Toxicol. 19, 244–255 (2005).
pubmed: 16173058
doi: 10.1002/jbt.20086
Giraudi, P. J., Bellarosa, C., Coda-Zabetta, C. D., Peruzzo, P. & Tiribelli, C. Functional induction of the cystine-glutamate exchanger system Xc(-) activity in SH-SY5Y cells by unconjugated bilirubin. PLoS ONE 6, e29078 (2011).
pubmed: 22216172
pmcid: 3246462
doi: 10.1371/journal.pone.0029078
Deganuto, M. et al. A proteomic approach to the bilirubin-induced toxicity in neuronal cells reveals a protective function of DJ-1 protein. Proteomics 10, 1645–1657 (2010).
pubmed: 20186750
doi: 10.1002/pmic.200900579
Qaisiya, M., Coda Zabetta, C. D., Bellarosa, C. & Tiribelli, C. Bilirubin mediated oxidative stress involves antioxidant response activation via Nrf2 pathway. Cell. Signal. 26, 512–520 (2014).
pubmed: 24308969
doi: 10.1016/j.cellsig.2013.11.029
Brini, M., Calì, T., Ottolini, D. & Carafoli, E. Neuronal calcium signaling: function and dysfunction. Cell Mol. Life Sci. 71, 2787–2814 (2014).
pubmed: 24442513
doi: 10.1007/s00018-013-1550-7
Watchko, J. F. Kernicterus and the molecular mechanisms of bilirubin-induced CNS injury in newborns. Neuromol. Med. 8, 513–529 (2006).
doi: 10.1385/NMM:8:4:513
Rodrigues, C. M. P. et al. Perturbation of membrane dynamics in nerve cells as an early event during bilirubin-induced apoptosis. J. Lipid Res. 43, 885–894 (2002).
pubmed: 12032163
doi: 10.1016/S0022-2275(20)30462-4
Brito, M. A., Brites, D. & Butterfield, D. A. A link between hyperbilirubinemia, oxidative stress and injury to neocortical synaptosomes. Brain Res. 1026, 33–43 (2004).
pubmed: 15476695
doi: 10.1016/j.brainres.2004.07.063
Hankø, E., Hansen, T. W. R., Almaas, R., Lindstad, J. & Rootwelt, T. Bilirubin induces apoptosis and necrosis in human NT2-N neurons. Pediatr. Res. 57, 179–184 (2005).
pubmed: 15611354
doi: 10.1203/01.PDR.0000148711.11519.A5
Zhang, B., Yang, X. & Gao, X. Taurine protects against bilirubin-induced neurotoxicity in vitro. Brain Res. 1320, 159–167 (2010).
pubmed: 20096270
doi: 10.1016/j.brainres.2010.01.036
Calligaris, R. et al. A transcriptome analysis identifies molecular effectors of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells. BMC Genom. 10, 543 (2009).
doi: 10.1186/1471-2164-10-543
Schiavon, E., Smalley, J. L., Newton, S., Greig, N. H. & Forsythe, I. D. Neuroinflammation and ER-stress are key mechanisms of acute bilirubin toxicity and hearing loss in a mouse model. PLoS ONE 13, e0201022 (2018).
pubmed: 30106954
pmcid: 6091913
doi: 10.1371/journal.pone.0201022
Qaisiya, M., Mardešić, P., Pastore, B., Tiribelli, C. & Bellarosa, C. The activation of autophagy protects neurons and astrocytes against bilirubin-induced cytotoxicity. Neurosci. Lett. 661, 96–103 (2017).
pubmed: 28965934
doi: 10.1016/j.neulet.2017.09.056
Verkhratsky, A. The endoplasmic reticulum and neuronal calcium signalling. Cell Calcium 32, 393–404 (2002).
pubmed: 12543098
doi: 10.1016/S0143416002001896
Dong, Z., Saikumar, P., Weinberg, J. M. & Venkatachalam, M. A. Calcium in cell injury and death. Annu Rev. Pathol. 1, 405–434 (2006).
pubmed: 18039121
doi: 10.1146/annurev.pathol.1.110304.100218
Qaisiya, M. et al. Bilirubin-induced ER stress contributes to the inflammatory response and apoptosis in neuronal cells. Arch. Toxicol. 91, 1847–1858 (2017).
pubmed: 27578021
doi: 10.1007/s00204-016-1835-3
Rauti, R., Qaisiya, M., Tiribelli, C., Ballerini, L. & Bellarosa, C. Bilirubin disrupts calcium homeostasis in neonatal hippocampal neurons: a new pathway of neurotoxicity. Arch. Toxicol. 94, 845–855 (2020).
pubmed: 32125443
doi: 10.1007/s00204-020-02659-9
Vaz, A. R. et al. Pro-inflammatory cytokines intensify the activation of NO/NOS, JNK1/2 and caspase cascades in immature neurons exposed to elevated levels of unconjugated bilirubin. Exp. Neurol. 229, 381–390 (2011).
pubmed: 21419123
doi: 10.1016/j.expneurol.2011.03.004
Rodrigues, C. M. P., Solá, S. & Brites, D. Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain neurons. Hepatology 35, 1186–1195 (2002).
pubmed: 11981769
doi: 10.1053/jhep.2002.32967
Silva, S. L. et al. Neuritic growth impairment and cell death by unconjugated bilirubin is mediated by NO and glutamate, modulated by microglia, and prevented by glycoursodeoxycholic acid and interleukin-10. Neuropharmacology 62, 2398–2408 (2012).
pubmed: 22361233
doi: 10.1016/j.neuropharm.2012.02.002
Fernandes, A. et al. Bilirubin as a determinant for altered neurogenesis, neuritogenesis, and synaptogenesis. Devel Neurobio 69, 568–582 (2009).
doi: 10.1002/dneu.20727
Chen, H. C., Tsai, D. J., Wang, C. H. & Chen, Y. C. An electron microscopic and radioautographic study on experimental kernicterus. I. Bilirubin transport via astroglia. Am. J. Pathol. 56, 31–58 (1969).
pubmed: 5815579
pmcid: 2013585
Silva, S. L. et al. Features of bilirubin-induced reactive microglia: from phagocytosis to inflammation. Neurobiol. Dis. 40, 663–675 (2010).
pubmed: 20727973
doi: 10.1016/j.nbd.2010.08.010
Gordo, A. C. et al. Unconjugated bilirubin activates and damages microglia. J. Neurosci. Res. 84, 194–201 (2006).
pubmed: 16612833
doi: 10.1002/jnr.20857
Vaz, A. R., Falcão, A. S., Scarpa, E., Semproni, C. & Brites, D. Microglia susceptibility to free bilirubin is age-dependent. Front. Pharmacol. 11, 1012 (2020).
pubmed: 32765258
pmcid: 7381152
doi: 10.3389/fphar.2020.01012
Brites, D. Bilirubin injury to neurons and glial cells: new players, novel targets, and newer insights. Semin. Perinatol. 35, 114–120 (2011).
pubmed: 21641483
doi: 10.1053/j.semperi.2011.02.004
Brites, D. The evolving landscape of neurotoxicity by unconjugated bilirubin: role of glial cells and inflammation. Front. Pharm. 3, 88 (2012).
doi: 10.3389/fphar.2012.00088
Fernandes, A., Falcão, A. S., Silva, R. F. M., Brito, M. A. & Brites, D. MAPKs are key players in mediating cytokine release and cell death induced by unconjugated bilirubin in cultured rat cortical astrocytes. Eur. J. Neurosci. 25, 1058–1068 (2007).
pubmed: 17331202
doi: 10.1111/j.1460-9568.2007.05340.x
Fernandes, A., Silva, R. F. M., Falcão, A. S., Brito, M. A. & Brites, D. Cytokine production, glutamate release and cell death in rat cultured astrocytes treated with unconjugated bilirubin and LPS. J. Neuroimmunol. 153, 64–75 (2004).
pubmed: 15265664
doi: 10.1016/j.jneuroim.2004.04.007
Blondel, S. et al. Vascular network expansion, integrity of blood–brain interfaces, and cerebrospinal fluid cytokine concentration during postnatal development in the normal and jaundiced rat. Fluids Barriers CNS 19, 47 (2022).
pubmed: 35672829
pmcid: 9172137
doi: 10.1186/s12987-022-00332-0
Mousa, A. & Bakhiet, M. Role of cytokine signaling during nervous system development. Int. J. Mol. Sci. 14, 13931–13957 (2013).
pubmed: 23880850
pmcid: 3742226
doi: 10.3390/ijms140713931
Barateiro, A. et al. Unconjugated bilirubin restricts oligodendrocyte differentiation and axonal myelination. Mol. Neurobiol. 47, 632–644 (2013).
pubmed: 23086523
doi: 10.1007/s12035-012-8364-8
Brito, M. A. et al. Cerebellar axon/myelin loss, angiogenic sprouting, and neuronal increase of vascular endothelial growth factor in a preterm infant with kernicterus. J. Child Neurol. 27, 615–624 (2012).
pubmed: 22190497
doi: 10.1177/0883073811423975
Barateiro, A., Domingues, H. S., Fernandes, A., Relvas, J. B. & Brites, D. Rat cerebellar slice cultures exposed to bilirubin evidence reactive gliosis, excitotoxicity and impaired myelinogenesis that is prevented by AMPA and TNF-α inhibitors. Mol. Neurobiol. 49, 424–439 (2014).
pubmed: 23982745
doi: 10.1007/s12035-013-8530-7
Falcão, A. S., Fernandes, A., Brito, M. A., Silva, R. F. M. & Brites, D. Bilirubin-induced immunostimulant effects and toxicity vary with neural cell type and maturation state. Acta Neuropathol. 112, 95–105 (2006).
pubmed: 16733655
doi: 10.1007/s00401-006-0078-4
Falcão, A. S., Fernandes, A., Brito, M. A., Silva, R. F. M. & Brites, D. Bilirubin-induced inflammatory response, glutamate release, and cell death in rat cortical astrocytes are enhanced in younger cells. Neurobiol. Dis. 20, 199–206 (2005).
pubmed: 16242628
doi: 10.1016/j.nbd.2005.03.001
Rodrigues, C. M. P., Solá, S., Silva, R. F. M. & Brites, D. Aging confers different sensitivity to the neurotoxic properties of unconjugated bilirubin. Pediatr. Res. 51, 112–118 (2002).
pubmed: 11756649
doi: 10.1203/00006450-200201000-00020
Jašprová, J. et al. Neuro-inflammatory effects of photodegradative products of bilirubin. Sci. Rep. 8, 7444 (2018).
pubmed: 29748620
pmcid: 5945592
doi: 10.1038/s41598-018-25684-2
Vodret, S. et al. Attenuation of neuro-inflammation improves survival and neurodegeneration in a mouse model of severe neonatal hyperbilirubinemia. Brain Behav. Immun. 70, 166–178 (2018).
pubmed: 29458193
doi: 10.1016/j.bbi.2018.02.011
Gazzin, S. et al. Curcumin prevents cerebellar hypoplasia and restores the behavior in hyperbilirubinemic gunn rat by a pleiotropic effect on the molecular effectors of brain damage. Int. J. Mol. Sci. 22, 299 (2021).
doi: 10.3390/ijms22010299
Arauchi, R. et al. Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test. Brain Behav. 8, e01028 (2018).
pubmed: 29953737
pmcid: 6085916
doi: 10.1002/brb3.1028
Limoa, E. et al. Electroconvulsive shock attenuated microgliosis and astrogliosis in the hippocampus and ameliorated schizophrenia-like behavior of Gunn rat. J. Neuroinflamm. 13, 230 (2016).
doi: 10.1186/s12974-016-0688-2
Liaury, K. et al. Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model. J. Neuroinflamm. 9, 56 (2012).
doi: 10.1186/1742-2094-9-56
Mahmoud, S., Gharagozloo, M., Simard, C. & Gris, D. Astrocytes maintain glutamate homeostasis in the CNS by controlling the balance between glutamate uptake and release. Cells 8, 184 (2019).
pubmed: 30791579
pmcid: 6406900
doi: 10.3390/cells8020184
Grojean, S., Koziel, V., Vert, P. & Daval, J. L. Bilirubin induces apoptosis via activation of NMDA receptors in developing rat brain neurons. Exp. Neurol. 166, 334–341 (2000).
pubmed: 11085898
doi: 10.1006/exnr.2000.7518
Grojean, S., Lievre, V., Koziel, V., Vert, P. & Daval, J.-L. Bilirubin exerts additional toxic effects in hypoxic cultured neurons from the developing rat brain by the recruitment of glutamate neurotoxicity. Pediatr. Res. 49, 507–513 (2001).
pubmed: 11264434
doi: 10.1203/00006450-200104000-00012
McDonald, J. W., Shapiro, S. M., Silverstein, F. S. & Johnston, M. V. Role of glutamate receptor-mediated excitotoxicity in bilirubin-induced brain injury in the Gunn Rat Model. Exp. Neurol. 150, 21–29 (1998).
pubmed: 9514835
doi: 10.1006/exnr.1997.6762
Granzotto, A., Canzoniero, L. M. T. & Sensi, S. L. A neurotoxic ménage-à-trois: glutamate, calcium, and zinc in the excitotoxic cascade. Front. Mol. Neurosci. 13, 600089 (2020).
pubmed: 33324162
pmcid: 7725690
doi: 10.3389/fnmol.2020.600089
Kaindl, A. M. & Ikonomidou, C. Glutamate antagonists are neurotoxins for the developing brain. Neurotox. Res. 11, 203–218 (2007).
pubmed: 17449460
doi: 10.1007/BF03033568
Lau, A. & Tymianski, M. Glutamate receptors, neurotoxicity and neurodegeneration. Pflug. Arch. - Eur. J. Physiol. 460, 525–542 (2010).
doi: 10.1007/s00424-010-0809-1
Riordan, S. M. & Shapiro, S. M. Review of bilirubin neurotoxicity I: molecular biology and neuropathology of disease. Pediatr. Res. 87, 327–331 (2020).
Wisnowski, J. L., Panigrahy, A., Painter, M. J. & Watchko, J. F. Magnetic resonance imaging of bilirubin encephalopathy: current limitations and future promise. Semin. Perinatol. 38, 422–428 (2014).
pubmed: 25267277
pmcid: 4250342
doi: 10.1053/j.semperi.2014.08.005
Das, S. & van Landeghem, F. K. H. Clinicopathological spectrum of bilirubin encephalopathy/kernicterus. Diagnostics 9, 24 (2019).
pubmed: 30823396
pmcid: 6468386
doi: 10.3390/diagnostics9010024
Nahar, L., Delacroix, B. M. & Nam, H. W. The role of parvalbumin interneurons in neurotransmitter balance and neurological disease. Front. Psychiatry 12, 679960 (2021).
pubmed: 34220586
pmcid: 8249927
doi: 10.3389/fpsyt.2021.679960
Shapiro, S. M. Chronic bilirubin encephalopathy: diagnosis and outcome. Semin Fetal Neonatal Med. 15, 157–163 (2010).
pubmed: 20116355
doi: 10.1016/j.siny.2009.12.004
Shapiro, S. M. & Riordan, S. M. Review of bilirubin neurotoxicity II: preventing and treating acute bilirubin encephalopathy and kernicterus spectrum disorders. Pediatr. Res. 87, 332–337 (2020).
Watchko, J. F. & Tiribelli, C. Bilirubin-induced neurologic damage — mechanisms and management approaches. N. Engl. J. Med. 369, 2021–2030 (2013).
pubmed: 24256380
doi: 10.1056/NEJMra1308124
Maisels, M. J. Neonatal hyperbilirubinemia and kernicterus - not gone but sometimes forgotten. Early Hum. Dev. 85, 727–732 (2009).
pubmed: 19833460
doi: 10.1016/j.earlhumdev.2009.09.003
Olusanya, B. O., Teeple, S. & Kassebaum, N. J. The contribution of neonatal jaundice to global child mortality: findings from the GBD 2016 study. Pediatrics 141, e20171471 (2018).
pubmed: 29305393
doi: 10.1542/peds.2017-1471
Shapiro, S. M. Definition of the clinical spectrum of kernicterus and bilirubin-induced neurologic dysfunction (BIND). J. Perinatol. 25, 54–59 (2005).
pubmed: 15578034
doi: 10.1038/sj.jp.7211157
Slusher, T. M. et al. Burden of severe neonatal jaundice: a systematic review and meta-analysis. BMJ Paediatr. Open 1, e000105 (2017).
pubmed: 29637134
pmcid: 5862199
doi: 10.1136/bmjpo-2017-000105
Daood, M. J., Hoyson, M. & Watchko, J. F. Lipid peroxidation is not the primary mechanism of bilirubin-induced neurologic dysfunction in jaundiced Gunn rat pups. Pediatr. Res. 72, 455–459 (2012).
pubmed: 22902434
doi: 10.1038/pr.2012.111
Geiger, A. S., Rice, A. C. & Shapiro, S. M. Minocycline blocks acute bilirubin-induced neurological dysfunction in jaundiced Gunn rats. Neonatology 92, 219–226 (2007).
pubmed: 17556840
doi: 10.1159/000103740
Lin, S. et al. Minocycline blocks bilirubin neurotoxicity and prevents hyperbilirubinemia-induced cerebellar hypoplasia in the Gunn rat. Eur. J. Neurosci. 22, 21–27 (2005).
pubmed: 16029192
doi: 10.1111/j.1460-9568.2005.04182.x
Smith, K. & Leyden, J. J. Safety of doxycycline and minocycline: a systematic review. Clin. Ther. 27, 1329–1342 (2005).
pubmed: 16291409
doi: 10.1016/j.clinthera.2005.09.005
Gourley, G. R. Bilirubin metabolism and kernicterus. Adv. Pediatr. 44, 173–229 (1997).
pubmed: 9265971
doi: 10.1016/S0065-3101(24)00052-5
Greco, C. et al. Diagnostic performance analysis of the point-of-care bilistick system in identifying severe neonatal hyperbilirubinemia by a multi-country approach. EClinicalMedicine 1, 14–20 (2018).
pubmed: 31193593
pmcid: 6537563
doi: 10.1016/j.eclinm.2018.06.003