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首页> 外文学位 >Brain derived neurotrophic factor: A foray into predicting neonatal outcomes in premature infants.
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Brain derived neurotrophic factor: A foray into predicting neonatal outcomes in premature infants.

机译：脑源性神经营养因子：尝试预测早产儿的新生儿结局。

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摘要

The need to accurately predict the ability of a prematurely born infant to recover from hypoxia induced damage associated with prematurity is rooted in our need to develop better interventions, with fewer side-effects, with which to treat these complicated patients. Previous work done in murine models mimicking hypoxia induced damage and its neurological sequelae have suggested hypoxia induced factor-1alpha; (HIF-1alpha), and its downstream effector molecules, brain derived neurotrophic factor (BDNF) and stromal derived factor-1 (SDF-1), may play an integral role in protecting the developing brain from the deleterious effects of low O2. Moreover, a number of single nucleotide polymorphisms (SNPs) have been identified, which affect the expression of these proteins on an individual basis. To that end, we hypothesized that BDNF expression levels gathered from venous cord blood, and genetic analysis for the presence of the rs6265 and rs1801157 SNPs in the BDNF and SDF-1 genes could be used as biochemical and genetic biomarkers to predict short term neonatal outcomes in premature infants born at Yale New Haven Hospital.;BDNF levels, determined by quantitative ELISA in 23 patients, and the presence of SNPs, determined in duplicate by restriction fragment length polymorphism assay and Sanger sequencing in 53 patients, were correlated with the development of a variety of neonatal outcomes. Our results indicated that although not statistically significant, the development of bronchopulmonary dysplasia, necrtotizing enterocolitis, and early onset neonatal sepsis (EONS) trended towards an association with lower cord blood BDNF levels (p-values <0.10). Likewise, the presence of the rs6265 SNP appeared to be protective against the development of culture positive EONS (p < 0.08), while the presence of rs1801157 SNP appeared to be protective against the development of clinical EONS. Taken together, these data suggest that while cord blood BDNF levels and the presence of the rs6265 and rs1801157 SNPs show potential as useful molecular and genetic biomarkers for predicting outcomes of premature infants, the association between these factors and neonatal outcomes is not strong enough for the number of patients examined in this study to provide conclusive results of the utility of these biomarkers in guiding clinical decision making. Consequently, further research of these, and other, biomarkers is necessary to better elucidate their usefulness.
机译：准确预测早产儿从缺氧引起的与早产相关的损害中恢复的能力的需求，源于我们需要开发出更好的干预措施，减少副作用以治疗这些复杂患者的需求。先前在模拟低氧诱导的损伤及其神经系统后遗症的小鼠模型中完成的研究表明，低氧诱导的因子-1α。 （HIF-1alpha）及其下游效应分子，脑源性神经营养因子（BDNF）和基质源性因子-1（SDF-1）可能在保护发育中的大脑免受低O2有害影响方面起着不可或缺的作用。此外，已经鉴定出许多单核苷酸多态性（SNP），它们会个别影响这些蛋白质的表达。为此，我们假设BDNF表达水平是从静脉血中收集的，并且对BDNF和SDF-1基因中rs6265和rs1801157 SNP的存在进行遗传分析可以用作生化和遗传生物标记物，以预测新生儿的短期结局Yale New Haven医院出生的早产儿；通过定量ELISA测定的23例患者中的BDNF水平，以及通过限制性片段长度多态性分析和Sanger测序确定的SNP的存在（一式两份）与53例患者的发生相关各种新生儿结局。我们的结果表明，尽管无统计学意义，但支气管肺发育不良，硬化性小肠结肠炎和早期发作的新生儿败血症（EONS）的发展趋向于与脐血BDNF水平降低相关（p值<0.10）。同样，rs6265 SNP的存在似乎可以防止培养阳性EONS的发生（p <0.08），而rs1801157 SNP的存在似乎可以防止临床EONS的发生。综上所述，这些数据表明，尽管脐带血BDNF水平以及rs6265和rs1801157 SNP的存在显示出作为预测早产儿结局的有用分子和遗传生物标记物的潜力，但这些因素与新生儿结局之间的关联性不足在这项研究中检查的患者数量，以提供这些生物标记物在指导临床决策中的实用性的最终结果。因此，有必要进一步研究这些以及其他生物标记，以更好地阐明其用途。

著录项

  • 作者

    Glinskii, Vladimir Vladislav.;

  • 作者单位

    Yale University.;

  • 授予单位 Yale University.;
  • 学科 Health Sciences Medicine and Surgery.;Health Sciences Human Development.;Biology Neuroscience.
  • 学位 M.D.
  • 年度 2013
  • 页码 59 p.
  • 总页数 59
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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