Brain Manganese Deposition in High Risk Neonates

高危新生儿脑锰沉积

• 批准号: 7103345
• 负责人: Judy Lynn Aschner
• 金额: $ 22.94万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-08 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7103345
• 关键词: bilirubin; bioimaging /biomedical imaging; brain imaging /visualization /scanning; brain metabolism; brain morphology; cholestasis; clinical research; developmental neurobiology; dietary supplements; environmental exposure; environmental toxicology; gestational age; human subject; infant human (0-1 year); infant nutrition disorder; iron metabolism; lenticular nucleus; liver disorder; longitudinal human study; magnetic resonance imaging; manganese; mass spectrometry; metal metabolism; metal poisoning; newborn human (0-6 weeks); nutrition related tag; parenteral feedings; white matter

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。过度的环境或饮食暴露会导致MN对大脑区域的MN沉积，从而导致心理和神经系统作用不良。需要肠胃外营养（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溶液中含有高浓度的MN，PN绕过正常的肠道吸收性控制和MN的胆汁排泄机制，并且婴儿是大脑发育的关键阶段。此外，由于MN和FE在中枢神经系统中竞争了相同的载体运输系统，因此铁（FE）缺乏症是病人新生儿中常见的问题，它增加了MN脑的吸收。该项目的长期目标是确定基于其胎龄，铁状态，肝功能和饮食MN的摄入量增加的新生儿种群，其脑MN沉积过多的风险增加，并提出基于证据的建议，以适当补充MN补充和监测接受PN的婴儿。该建议将通过40名接受MN支持的PN和10名对照婴儿的新生儿中的磁共振成像（MR）成像研究MN的大脑沉积（MR）成像。两个具体目的将检验以下假设：（1）在接收PN的新生儿中选择性Mn敏感大脑区域中MR T1和T2松弛时间（MN标记）的缩短将直接与（a）饮食中的MN摄入量相关，（a）Pn（b）Pn（b）通过（c）通过（C）通过（C）测量的Plass pplass plassmame（c），（c）测量的plassma-specper（c）plassma speceds proppers pplespect speceptrence（d）功能障碍/胆汁淤积（通过共轭胆红素水平评估）。 （2）T1和T2松弛时间的缩短将与（a）胎龄和（b）Fe状态相关（由血清Fe，铁蛋白，转移蛋白，可溶性转移蛋白受体和血红蛋白评估）。脑MN在婴儿中的积累增加的潜力以及与脑MN负担增加有关的潜在健康风险代表了至关重要的，未开发的暴露和敏感性问题。饮食中的MN，尤其是育儿MN的影响，胎龄，Fe状态和肝功能障碍对新生儿大脑调节MN沉积的能力的影响尚未得到科学解决。拟议的临床研究具有巨大的健康意义，并可能阐明婴儿和儿童长期肠胃外营养中神经功能障碍的发展和进展。