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，尽管在产科和新生儿护理方面取得了重大进展，但每年仍有大约100万新生儿死亡。最近的研究表明，将新生儿脑损伤的婴儿降温至33.5摄氏度，持续72小时，这一过程被称为治疗性低温(TH)，可以显著减少约50%受影响婴儿的脑损伤。然而，对于出生时有前哨事件和MRI上有基底节损伤的新生儿，它似乎比MRI上发现的血管间边界区(分水岭)损伤的新生儿更有效。TH减少脑损伤的确切机制和治疗对某些婴儿有效而对其他婴儿无效的原因都不清楚。众所周知，新生儿脑损伤具有多种特征，可能还有不同的机制。因此，根据损伤类型和对初始治疗的反应，最终可能会针对不同的婴儿量身定制不同的治疗方法。这项研究建议在新生儿期使用磁共振成像技术，称为扩散张量成像(DTI)和质子磁共振波谱(MRS)，以评估哪些类型的损伤对TH反应最好。与之前没有TH的研究相比，这个队列中6个月大的以后的MRI研究将使用更复杂的方法来评估损伤的严重程度，以及在TH的帮助下身体修复损伤的能力有多好。最后，核磁共振扫描将在8-10岁时从早期研究中登记的患者身上获得。有非常相似损伤的儿童将被归类在一起，核磁共振结果将被用来看看在受伤恢复得最好的儿童身上发现了什么MRI特征(使用更复杂的MRI方法)，而在那些恢复得不好的儿童身上发现了什么。这些MRI特征将被指定为新生儿损伤后大脑修复的标志。了解这些标记物将有助于更快地评估用于促进新生儿脑损伤后修复的新的治疗干预措施。