Repair After Ischemic in the Term Newborn

足月新生儿缺血后的修复

• 批准号: 8653645
• 负责人: James Barkovich
• 金额: $ 18.3万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653645
• 关键词: 10 year old; Adjuvant Therapy; Affect; Age; Animals; Apoptotic; Area; Basal Ganglia; Birth; Brain; Brain Injuries; Caring; Cell Death; Cell Death Process; Cells; Characteristics; Child; Chronic; Clinical; Data; Diffusion Magnetic Resonance Imaging; Discipline of obstetrics; Encephalopathies; Energy Metabolism; Enrollment; Erythropoietin; Event; Evolution; Failure; Hour; Hybrids; Hypoxia; Image; Impairment; Incidence; Individual; Infant; Inflammation; Injury; Intervention; Ischemia; Knowledge; Length; MRI Scans; Magnetic Resonance; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Metabolism; Methods; Metric; Monitor; Natural regeneration; Necrosis; Neonatal; Neonatal Brain Injury; Nerve Regeneration; Neurons; Newborn Infant; Outcome; Patients; Pattern; Perfusion; Phase; Population; Prevalence; Process; Protons; Recovery; Scanning; Sentinel; Severities; Spin Labels; Staging; Study Subject; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Treatment Effectiveness; base; brain repair; cell injury; cohort; early onset; improved; injury and repair; intervention effect; natural hypothermia; neonatal death; neonate; novel therapeutic intervention; programs; repaired; response; response to injury; white matter

Neonatal encephalopathy and associated brain injury is a serious problem that results in an estimated 1 million annual neonatal deaths despite major advances in obstetrics and neonatal care. Recent studies have shown that cooling babies who suffer neonatal brain injury to 33.5¿ C for 72 hours, a process known as Therapeutic Hypothermia (TH), can markedly reduce brain injury in about 50% of affected babies. However, it appears to be more effective in neonates who have a sentinel event at the time of birth and basal ganglia injury on MRI than in those with intervascular boundary zone ("watershed") injury identified on MRI. Neither the exact mechanisms by which TH reduces brain injury nor the reasons that the treatment is effective in some babies but not others are understood. It is known that neonatal brain injuries have a mixture of characteristics and, probably different mechanisms. Therefore, different treatments might eventually be tailored to individual babies based upon the type of injury and response to initial therapy. This study proposes to use techniques involving magnetic resonance imaging, called diffusion tensor imaging (DTI) and proton MR spectroscopy (MRS) in the neonatal period to assess which types of injury respond best to TH. A later MRI study at age 6 months from this cohort will use more sophisticated methods to evaluate how severe the injury was and how well the body was able to repair the injury with the help of TH as compared to prior studies without TH. Finally, MRI scans will be obtained at ages of 8-10 years from patients that were enrolled in an earlier study. Children who had very similar injuries will be grouped together and the MRI results will be used to see what MRI characteristics (using the more sophisticated MRI methods) are found in the children who recovered best from their injury but not in those who did not recover well. These MRI characteristics will be designated as "markers of brain repair" after neonatal injury. Knowledge of these markers will help to more quickly evaluate new therapeutic interventions being used to increase repair after neonatal brain injury.

新生儿脑病和相关的脑损伤是一个严重的问题，估计导致每年100万例新生儿死亡的妇产科和新生儿护理的重大进展。最近的研究表明，在72小时内遭受新生儿脑损伤的冷却婴儿，这一过程称为治疗性体温过低（Th），可以显着减少约50％的受影响婴儿的脑损伤。但是，与在MRI上发现的哨兵损伤的新生儿中，在出生时发生哨兵事件的新生儿和对MRI的基本神经节损伤的有效性更高。既不是降低脑损伤的确切机制，也不是对某些婴儿有效但没有理解治疗有效的原因。众所周知，新生儿脑损伤具有特征和可能不同的机制的混合物。因此，根据损伤类型和对初始治疗的反应，可能最终针对个体婴儿量身定制不同的治疗方法。这项研究建议在新生儿时期使用涉及磁共振成像的技术，称为差异张量成像（DTI）和质子MR光谱法（MRS）来评估哪种损伤类型对TH的反应最佳。与没有TH的先前研究相比，该队列中6个月以后的MRI研究将使用更复杂的方法来评估受伤的严重程度以及人体能够借助TH修复损伤的能力。最后，将从参加早期研究的患者的8-10岁年龄段获得MRI扫描。患有非常相似伤​​害的儿童将被分组在一起，MRI结果将用于查看在儿童中发现什么MRI特征（使用更复杂的MRI方法），他们从受伤中恢复最佳，但在那些恢复不佳的孩子中却没有。这些MRI特征将被指定为新生儿损伤后的“脑修复标记”。这些标记的知识将有助于更快地评估新的治疗干预措施，以增加新生儿脑损伤后修复。