期刊
JOURNAL OF CHILD NEUROLOGY
卷 27, 期 5, 页码 615-624出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0883073811423975
关键词
angiogenesis; kernicterus; multidrug resistance-associated protein 1; neuronal impairment; vascular endothelial growth factor
资金
- Fundacao para a Ciencia e a Tecnologia, Portugal [PTDC/SAU-FCF/68819/2006, PTDC/SAU-NEU/64385/2006]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-NEU/64385/2006, PTDC/SAU-FCF/68819/2006] Funding Source: FCT
We performed histologic and immunohistochemical analysis of cerebellar sections from a preterm infant (32 weeks 5 days) dead on the 4th day of life with the diagnosis of kernicterus and compared the results with 1 age-matched nonicteric patient. Poorer Luxol fast blue-periodic acid Schiff and Bodian-Luxol fast blue stainings as well as neurofilament expression were observed in the kernicterus case, indicating loss of axon neurites and myelin fibers. Elevated claudin-5 and cluster of differentiation 34 expression associated with increased blood vessel density suggests bilirubin-induced angiogenic sprouting. Upregulation of vascular endothelial growth factor and its receptor 2 was observed in nucleus dentatus and Purkinje neurons. Although upregulation of multidrug resistance-associated protein 1 was increased in cerebellar neurons, it was not able to prevent bilirubin-induced neurotoxicity. These data add new insights into the pathophysiology of kernicterus, revealing vascular endothelial growth factor and its receptor 2, as well as angiogenic sprouting, as new players in neurologic damage by unconjugated bilirubin.
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