CSF LEVELS OF L1CAM AND AMYLOID PRECURSOR PROTEIN IN POST-HEMORRHAGIC HYDROCEPHAL

出血后脑积水脑脊液中 L1CAM 和淀粉样前体蛋白的水平

• 批准号: 8460508
• 负责人: David Delmar Limbrick
• 金额: $ 17.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8460508
• 关键词: Affect; Aftercare; Age; Amyloid beta-Protein Precursor; Atrophic; Biology; Cannulations; Caring; Cephalic; Cerebral Palsy; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Childhood; Clinical Research; Clinical Treatment; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Complement; Complication; Consensus; Creation of ventriculo-peritoneal shunt; Data; Development; Devices; Feedback; Hydrocephalus; Image; Implant; Individual; Infant; Infant Development; Injury; Interdisciplinary Study; K-Series Research Career Programs; Laboratories; Language; Measurement; Measures; Medicine; Mentors; Motor; Neonatal; Nerve Degeneration; Nervous System Trauma; Neural Cell Adhesion Molecule L1; Neurites; Neurologic; Neurological outcome; Neurosurgeon; Newborn Infant; Outcome; Pathogenesis; Pediatric Hospitals; Physicians; Play; Population; Premature Birth; Premature Infant; Process; Proteins; Proteomics; Recruitment Activity; Regression Analysis; Regulation; Relative (related person); Research; Research Methodology; Research Training; Role; Sampling; Scientist; Seizures; Spinal Puncture; Time; Training; Treatment Effectiveness; Ultrasonography; United States National Institutes of Health; Universities; Variant; Ventricular; Very Low Birth Weight Infant; Washington; base; career development; cohort; disability; implantation; improved; infant outcome; interest; intraventricular hemorrhage; nervous system disorder; neurodevelopment; novel marker; premature; prevent; programs; repository; skills training; synaptogenesis; tool; white matter; Affect; Aftercare; Age; Amyloid beta-Protein Precursor; Atrophic; Biology; Cannulations; Caring; Cephalic; Cerebral Palsy; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Childhood; Clinical Research; Clinical Treatment; Clinical Trials; Cognition; Cognitive; Cognitive deficits; Complement; Complication; Consensus; Creation of ventriculo-peritoneal shunt; Data; Development; Devices; Feedback; Hydrocephalus; Image; Implant; Individual; Infant; Infant Development; Injury; Interdisciplinary Study; K-Series Research Career Programs; Laboratories; Language; Measurement; Measures; Medicine; Mentors; Motor; Neonatal; Nerve Degeneration; Nervous System Trauma; Neural Cell Adhesion Molecule L1; Neurites; Neurologic; Neurological outcome; Neurosurgeon; Newborn Infant; Outcome; Pathogenesis; Pediatric Hospitals; Physicians; Play; Population; Premature Birth; Premature Infant; Process; Proteins; Proteomics; Recruitment Activity; Regression Analysis; Regulation; Relative (related person); Research; Research Methodology; Research Training; Role; Sampling; Scientist; Seizures; Spinal Puncture; Time; Training; Treatment Effectiveness; Ultrasonography; United States National Institutes of Health; Universities; Variant; Ventricular; Very Low Birth Weight Infant; Washington; base; career development; cohort; disability; implantation; improved; infant outcome; interest; intraventricular hemorrhage; nervous system disorder; neurodevelopment; novel marker; premature; prevent; programs; repository; skills training; synaptogenesis; tool; white matter

DESCRIPTION (provided by applicant): The candidate for this Career Development Award (CDA) is a pediatric neurosurgeon with a specific interest in advancing the field of post-hemorrhagic hydrocephalus of prematurity (PHH) and improving the care and outcomes of infants with this condition. The rigorous career development program outlined in this proposal has both didactic components and mentored scientific training in the laboratories of Drs. Terrie Inder and David Holtzman at Washington University. The proposed program builds on the strengths of the University's NIH-supported interdisciplinary research centers and the Clinical Research Training Center to focus the candidate's training on clinical research methodologies, cerebrospinal fluid (CSF) protein biology, and neurodevelopment and disability in the preterm infant. The additional training and skills acquired through this CDA will complement the candidate's previous research background and provide new expertise necessary to become an independent clinician-scientist. The central hypotheses of this proposal are that CSF levels of the neurodevelopment proteins L1CAM and amyloid precursor protein (APP) are selectively increased in PHH, and that protracted elevations of these proteins are associated with increased ventricular size, ventriculoperitoneal (VP) shunt requirement, and adverse neurological outcome. The Specific Aims of this proposal are to: 1) compare the levels of CSF L1CAM and APP in control, PHH, and other neurological conditions; 2) define the association between CSF L1CAM and APP and ventricular size in PHH; and 3) determine the relationship of PHH-associated CSF L1CAM and APP elevations to neurodevelopment outcomes at 18-24 months corrected age. The candidate proposes to leverage his participation in the Hydrocephalus Clinical Research Network to establish a multi- institutional neonatal CSF repository at Washington University. CSF levels of L1CAM and APP in PHH will be measured using ELISAs and compared with those in intraventricular hemorrhage and other neurological conditions common to preterm infants. The association between these CSF proteins and ultrasound-based measures of ventricular size will defined, and the relative gains afforded by CSF L1CAM and APP in identifying infants that require VP shunts will be estimated. Finally, the relationship between CSF L1CAM and APP levels and neurodevelopment outcome will be determined using Bayley Scales of Infant Development-III scoring at 18-24 months corrected age. If successful, these studies will advance the field of PHH by providing crucial data for the development of CSF L1CAM and APP levels as markers of PHH-associated neurological disability. The most immediate benefit of these markers would be to complement existing image-based ventricular measures to better inform clinical trials directed at improving the outcomes of infants with PHH.

描述（由申请人提供）：该职业发展奖（CDA）的候选人是一种儿科神经外科医生，对提高早产后脑电图（PHH）的领域具有特别的兴趣，并改善了具有这种情况的婴儿的护理和结果。该提案中概述的严格的职业发展计划既具有教学成分，又有DRS实验室的科学培训。华盛顿大学的Terrie Inder和David Holtzman。拟议的计划基于大学NIH支持的跨学科研究中心和临床研究培训中心的优势，将候选人的培训集中在临床研究方法上，脑脊液（CSF）蛋白质生物学，以及早体婴儿的神经发育和残疾。通过此CDA获得的额外培训和技能将补充候选人以前的研究背景，并提供成为独立临床医生的新专业知识。 该提案的中心假设是，神经发育蛋白L1CAM和淀粉样蛋白前体蛋白（APP）的CSF水平有选择地增加，并且这些蛋白质的长期升高与心室尺寸增加有关，脑室脑（VP）Shunt shunt Shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt shunt和反应。该提案的具体目的是：1）比较控制，PHH和其他神经系统状况的CSF L1CAM和APP的水平； 2）定义CSF L1CAM与APP之间的关联以及PHH中的心室大小； 3）确定与PHH相关的CSF L1CAM与APP升高与校正年龄18-24个月的神经发育结果的关系。候选人建议利用他参与脑积水临床研究网络，以在华盛顿大学建立一个多机构的新生儿CSF存储库。 PHH中的L1CAM和APP的CSF水平将使用ELISA进行测量，并与脑室内出血和早产儿共同的其他神经系统疾病进行比较。这些CSF蛋白与心室大小的超声测量之间的关联将定义，并且CSF L1CAM和APP在识别需要VP分流器的婴儿方面所获得的相对收益将得到估计。最后，CSF L1CAM与APP水平与神经发育结果之间的关系将使用婴儿发育的Bayley量表在18-24个月校正年龄的III-III-III评分。如果成功，这些研究将通过提供CSF L1CAM和APP水平作为PHH相关神经障碍的标志的重要数据来推进PHH领域。这些标记的最直接好处是补充现有的基于图像的心室措施，以更好地告知旨在改善PHH婴儿结果的临床试验。