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Brain Manganese Deposition in High Risk Neonates

高危新生儿脑锰沉积

基本信息

批准号：
7244111
负责人：
Judy Lynn Aschner
金额：
$ 18.63万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-06-08 至 2009-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7244111
关键词：
Address Age Age-Months Base of the Brain Biliary Bilirubin Birth Blood Brain Brain region Bypass Child Cholestasis Chromium Clinical Trials Control Groups Copper Coupled Deposition Detection Development Elements Enteral Exposure to Ferritin Functional disorder Gestational Age Globus Pallidus Goals Growth and Development function Health Hemoglobin Hepatic Hour Infant Intake Intestines Iron Light Magnetic Resonance Magnetic Resonance Imaging Manganese Maps Mass Spectrum Analysis Measurement Measures Metals Minerals Modeling Neonatal Neonatal Intensive Care Units Neuraxis Neurologic Neurologic Dysfunctions Numbers Parental Consent Parenteral Nutrition Pediatric Hospitals Pilot Projects Plasma Population Predisposition Prematurity of fetus Recruitment Activity Relaxation Research Design Risk Serum Solutions Staging Study Subject Supplementation System Techniques Testing Time Trace Elements Transferrin Transferrin Receptor Vulnerable Populations Week Whole Blood Zinc base day evidence based guidelines infant monitoring neonate neurotoxicity nutrition postnatal psychologic sound uptake white matter

项目摘要

DESCRIPTION (provided by applicant): Manganese (Mn) is an essential metal needed for normal growth and development. Excessive environmental or dietary exposure results in Mn deposition in Mn-sensitive brain regions causing adverse psychological and neurological effects. Sick infants requiring parenteral nutrition (PN) may be at increased risk of Mn neurotoxicity because neonatal PN solutions contain high concentrations of Mn, PN bypasses the normal intestinal absorptive control and biliary excretory mechanisms for Mn, and infants are at a critical stage of brain development. Furthermore, iron (Fe) deficiency, a common problem among sick neonates, increases Mn brain uptake because Mn and Fe compete for the same carrier transport systems in the central nervous system. The long term goals of this project are to identify neonatal populations that are at increased risk of excessive brain Mn deposition based on their gestational age, iron status, hepatic function and dietary Mn intake, and to make evidence-based recommendations for appropriate Mn supplementation and monitoring of infants receiving PN. This proposal will investigate brain deposition of Mn, a paramagnetic element, by magnetic resonance (MR) imaging in 40 neonates receiving Mn-supplemented PN and 10 control infants. Two specific aims will test the following hypotheses: (1) shortening of MR T1 and T2 relaxation times (a marker for Mn) in selective Mn-sensitive brain regions in neonates receiving PN will correlate directly with (a) dietary Mn intake, (b) days on PN, (c) blood Mn levels (measured by Inductively Coupled Plasma-Mass Spectrometry) and (d) hepatic dysfunction/cholestasis (assessed by conjugated bilirubin levels). (2) shortening of T1 and T2 relaxation times will correlate inversely with (a) gestational age and (b) Fe status (assessed by serum Fe, ferritin, transferrin, soluble transferrin receptor and hemoglobin). The potential for increased brain Mn accumulation in infants and the potential health risks associated with elevated brain Mn burden represent crucial, unexplored issues of exposure and susceptibility. The impact of dietary Mn, and especially parenterally delivered dietary Mn, gestational age, Fe status, and hepatic dysfunction on the ability of the neonatal brain to regulate Mn deposition has not been scientifically addressed. The proposed clinical investigation has enormous health significance and may shed light on the development and progression of neurological dysfunction in infants and children on prolonged parenteral nutrition.

描述（由申请人提供）：锰（Mn）是正常生长和发育所需的必需金属。过量的环境或饮食暴露导致锰沉积在锰敏感的大脑区域，造成不良的心理和神经影响。需要肠外营养（PN）的患病婴儿可能会增加Mn神经毒性的风险，因为新生儿PN溶液含有高浓度的Mn，PN绕过了Mn的正常肠道吸收控制和胆汁排泄机制，并且婴儿处于大脑发育的关键阶段。此外，铁（Fe）缺乏症是患病新生儿的常见问题，会增加Mn的脑摄取，因为Mn和Fe在中枢神经系统中竞争相同的载体转运系统。该项目的长期目标是根据胎龄、铁状态、肝功能和膳食锰摄入量确定脑锰沉积过度风险增加的新生儿人群，并为接受PN的婴儿提供适当的锰补充和监测的循证建议。本提案将通过磁共振（MR）成像研究40例接受Mn补充PN的新生儿和10例对照婴儿的Mn（一种顺磁性元素）脑沉积。两个具体目标将检验以下假设：（1）接受PN的新生儿选择性锰敏感脑区中MR T1和T2弛豫时间（锰的标志物）的缩短将与（a）膳食锰摄入量，（B）PN天数，（c）血液锰水平（通过电感耦合等离子体质谱法测量）和（d）肝功能障碍/胆汁淤积（通过结合胆红素水平评估）直接相关。(2)T1和T2弛豫时间的缩短将与（a）胎龄和（B）Fe状态（通过血清Fe、铁蛋白、转铁蛋白、可溶性转铁蛋白受体和血红蛋白评估）负相关。婴儿脑锰蓄积增加的可能性以及与脑锰负荷升高相关的潜在健康风险代表了暴露和易感性的关键、未探索的问题。饮食锰，特别是肠道外提供的饮食锰，胎龄，铁状态，肝功能障碍的新生儿大脑的能力，以调节锰沉积的影响还没有得到科学的解决。拟议的临床研究具有巨大的健康意义，并可能揭示长期肠外营养的婴儿和儿童神经功能障碍的发展和进展。