ROLE OF EXTRACELLULAR MATRIX IN HYPOXIC-ISCHEMIC PERINATAL WHITE MATTER INJURY

细胞外基质在围产期缺氧缺血性脑白质损伤中的作用

• 批准号: 8173210
• 负责人: Larry S. Sherman
• 金额: $ 5.71万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173210
• 关键词: Acute; Astrocytosis; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Cerebral Palsy; Cerebrum; Cessation of life; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Extracellular Matrix; Funding; Gliosis; Glycosaminoglycans; Grant; Human; Hyaluronan; Hypoxia; Institution; Life; Neurologic; Perinatal; Periventricular white matter injury; Premature Birth; Rattus; Research; Research Personnel; Residual state; Resources; Role; Source; Survivors; Testing; United States National Institutes of Health; disability; fetal infection; myelination; neurovascular unit; novel; premature; prevent; white matter; white matter injury

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human periventricular white matter injury (PWMI) is the predominant form of brain damage and the leading cause of life-long neurological disability from cerebral palsy in survivors of premature birth. In the premature human brain there is a window of vulnerability when hypoxia-ischemia (H-l), maternal-fetal infection and other insults damage cerebral white matter. We propose to define novel mechanisms in perinatal rat and human by which acute white matter injury leads to disruptions in the neurovascular unit at the level of the extracellular matrix that disrupt normal myelinogenesis. We will test the overall hypothesis that the predilection of the preterm white matter to chronic myelination disturbances after H-l is related to the acute degeneration of preOLs that triggers chronic reactive astrocytosis. Our preliminary data suggest that reactive gliosis leads to the accumulation of the glycosaminoglycan hyaluronan (HA) and that HA can block preOL maturation. We hypothesize that reactive astrocytosis prevents the normal maturation of the residual pool of susceptible preOLs, arrests normal myelination and results in a persistent state of increased vulnerability of the white matter with delayed preOL death through a mechanism that involves HA accumulation.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 人脑周围白质损伤（PWMI）是脑损伤的主要形式，也是早产幸存者脑瘫的终生神经疾病的主要原因。在过早的人脑中，当缺氧 - 缺血（H-L），母亲感染和其他侮辱损害大脑白质时，存在一个脆弱性的窗口。我们建议在围产期大鼠和人类中定义新的机制，急性白质损伤导致神经血管单位的破坏在细胞外基质水平上破坏正常骨髓纤维化的作用。我们将测试总体假设，即在H-L之后，早产白质对慢性髓鞘紊乱的偏见与触发慢性反应性星形胶质细胞增多的preols的急性变性有关。我们的初步数据表明，反应性神经病会导致糖胺聚糖透明质酸（HA）的积累，并且HA可以阻止Preol成熟。我们假设反应性星形细胞增多症可以防止易感普雷醇的残留池的正常成熟，阻止正常的髓鞘形成，并通过涉及HA积累的机制延迟preol死亡，导致白质的脆弱性增加，导致白质的脆弱性增加。