Are the neuromotor disabilities of bilirubin-induced neurologic dysfunction disorders related to the cerebellum and its connections?

Watchko, Jon F.; Painter, Michael J.; Panigrahy, Ashok

doi:10.1016/j.siny.2014.12.004

Cited by 11 publications

(9 citation statements)

References 60 publications

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“…Cll hypoplasia is a hallmark of hyperbilirubinemia in rodents 26 – 29 , and cerebellar involvement with morphological and behavioral abnormalities has also been reported in severely hyperbilirubinemic neonates 30 – 32 . Inflammation and oxidative stress are considered the major mechanisms of bilirubin neurotoxicity, whereas the impact of hyperbilirubinaemia on CNS development has been only marginally envisaged, and evaluated mostly by in vitro experiments 33 , 34 .…”

Section: Discussionmentioning

confidence: 99%

Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat

Vianello

Zampieri

Marcuzzo

et al. 2018

Sci Rep

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Bilirubin neurotoxicity has been studied for decades and has been shown to affect various mechanisms via significant modulation of gene expression. This suggests that vital regulatory mechanisms of gene expression, such as epigenetic mechanisms, could play a role in bilirubin neurotoxicity. Histone acetylation has recently received attention in the CNS due to its role in gene modulation for numerous biological processes, such as synaptic plasticity, learning, memory, development and differentiation. Aberrant epigenetic regulation of gene expression in psychiatric and neurodegenerative disorders has also been described. In this work, we followed the levels of histone 3 lysine 14 acetylation (H3K14Ac) in the cerebellum (Cll) of the developing (2, 9, 17 days after the birth) and adult Gunn rat, the natural model for neonatal hyperbilirubinemia and kernicterus. We observed an age-specific alteration of the H3K14Ac in the hyperbilirubinemic animals. The GeneOntology analysis of the H3K14Ac linked chromatin revealed that almost 45% of H3K14Ac ChiP-Seq TSS-promoter genes were involved in CNS development including maturation and differentiation, morphogenesis, dendritogenesis, and migration. These data suggest that the hallmark Cll hypoplasia in the Gunn rat occurs also via epigenetically controlled mechanisms during the maturation of this brain structure, unraveling a novel aspect of the bilirubin-induced neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat

Vianello

Zampieri

Marcuzzo

et al. 2018

Sci Rep

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“…9e11 Chronic bilirubin encephalopathy mainly affects subcortical areas, such as the globus pallidus, subthalamus, substantia nigra, cerebellar dentate nucleus, or hippocampus, although the underlying mechanisms are still unknown. 12,13 Some scholars believe that the pathological mechanisms of bilirubin encephalopathy involve the deposition of bilirubin, which leads to increased neuronal Ca 2þ influx, which in turn increases the excitability of proteolytic enzymes and leads to neuronal apoptosis. 14 The majority of children with acute bilirubin encephalopathy recover if serum bilirubin levels are reduced with timely treatment, and only a few have sequelae, such as nuclear jaundice.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia

Yan

Han

Ren

et al. 2018

Pediatrics & Neonatology

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“…Although, the underlying mechanisms are still unknown [16,17] . Most of ABE neonatal patients still have a chance to be recovered by timely treatment of reducing serum bilirubin levels, while only a few suffer from sequelae, like kernicterus.…”

Section: Discussionmentioning

confidence: 99%

Analysis on the MRI and BAEP Results of Neonatal Brain with Different Levels of Bilirubin

Zhongxing

Ding

Wang

et al. 2020

Preprint

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Background：To explore whether there is abnormality of neonatal brains’ MRI and BAEP with different bilirubin levels, and to provide an objective basis for early diagnosis on the bilirubin induced subclinical damage on brains.Methods: To retrospectively analyze the clinical data of 103 neonatal patients, who had been hospitalized in Neonatology Department of Taicang First People’s Hospital from March 2013 to September 2015, to conduct routine brain MRI examination , BAEP testing and to analyze BAEP and MRI image results of the neonatal patients, who were divided into three groups based on the levels of total serum bilirubin concentration (TSB), 16 cases in mild group (TSB:0.0~229.0μmol/L), 49 cases in moderate group (TSB: 229.0~342.0μmol/L) and 38 cases in severe group (TSB≥342.0μmol/L); Results: We found as follows: A. Comparison of the bilirubin value of the different group : 1. The bilirubin value of the mild group is 171.99±33.50 μmol/L, the moderate group is293.98±32.09 μmol/L, and the severe group is 375.59±34.25 μmol /L . And the comparison of bilirubin values of the three groups of neonates (P＜0.01) indicates the difference is statistically significant (P＜0.01). 2. The bilirubin value of the pre-term group is 289.70±85.38μmol/Land the full-term group is 310.36±72.32 μmol/L, but the comparison of the bilirubin values between pre-term group and full-term group indicates that the difference is not statistically significant (P＞0.05).3. The bilirubin value of the normal brain MRI group(82) is 305.55±74.54 μmol/L and the abnormal brain MRI group is 303.56±83.04μmol/L; the comparison of bilirubin values between the two groups indicates that the difference is not statistically significant(P＞0.05). B. The weight value of the ﹤2500g group is 2.04±0.21 and the ≥2500ggroup is 3.39±0.46; the weight comparison of the two groups indicates that the difference is statistically significant (P＜0.01). C. Comparison of the abnormal MRI of the different groups: 1.The brain MRI result's abnormal ratio of the mild group is 31.25%, the moderate group is 16.33% and the severe group is 21.05%, but the comparison of brain MRI results of the three neonates groups indicates that the difference is not statistically significant (P＞0.05). 2.The brain MRI result's abnormal ratio of the pre-term is 30.77% and the full-term group is 16.88%, but the comparison of brain MRI results between prem-term group and full-term group indicates that the difference is not statistically significant (P＞0.05). 3.The brain MRI result's abnormal ratio of the ﹤2500g group is 37.50% and the ≥2500g group is 17.24%; but the comparison of brain MRI results of two neonates groups indicates that the difference is not statistically significant(P＞0.05). D. Comparison of abnormal MRI signal values of globus pallidus on T1WI in different groups: 1. The comparison of normal group signal values with that of mild group (p < 0.05), with that of moderate group and with that of severe group (p < 0.01) indicates that the difference is statistically significant; 2. The comparison of signal values between mild and moderate groups (p < 0.05) and between mild group and severe group (p < 0.01) indicates that the difference is statistically significant; 3. The comparison of signal values between moderate group and severe group indicates that the difference is statistically significant(p < 0.05). E. Comparison of BAEP testing results in groups: 1. There were 27(26.21%) cases in abnormalities of the BAEP results of all 103cases bilirubin patients. 2. There were 15(18.29%) cases in abnormalities of the BAEP result of the 82 cases normal brain MRL , 2(40%) cases in abnormalities of the BAEP result of the 5 cases abnormal MRI in mild bilirubin group, 4（50%） cases in abnormalities of the BAEP result of the 8 cases abnormal MRI in moderate bilirubin group and 6（75%）cases in abnormalities of the BAEP result of the 8 cases abnormal brain MRI in severe bilirubin group. 3. After one month review of the BAEP result, there was 0（0.00%） abnormal case in the normal MRI and the mild group; there were 1（20%） abnormal case in the moderate group and 2（25%） cases in the severe group. Conclusion: At low level of bilirubin, central nervous system damage may also occur and can be detected as abnormality by MRI and BAEP. Meanwhile, MRI and BAEP can also provide early abnormal information for the judgment of central nervous system damage of the children with NHB who have no acute bilirubin encephalopathy (ABE) clinical features, and provide clues for early treatment and early intervention.

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Are the neuromotor disabilities of bilirubin-induced neurologic dysfunction disorders related to the cerebellum and its connections?

Cited by 11 publications

References 60 publications

Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat

Histone acetylation as a new mechanism for bilirubin-induced encephalopathy in the Gunn rat

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia

Analysis on the MRI and BAEP Results of Neonatal Brain with Different Levels of Bilirubin

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