A novel ferret model of preterm encephalopathy

一种新型雪貂早产脑病模型

• 批准号: 9111076
• 负责人: Sandra E Juul
• 金额: $ 19.31万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111076
• 关键词: Acute; Affect; Animal Model; Animals; Antibodies; Architecture; Birth; Blood Vessels; Blood specimen; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Cerebral Palsy; Cerebral hemisphere hemorrhage; Chronic; Cognition; Complex; Data; Development; Disease; Electroencephalography; Encephalopathies; Endotoxins; Ensure; Event; Exposure to; Ferrets; Genetically Modified Animals; Glycerol; Goals; Gray unit of radiation dose; Growth; Growth and Development function; Health; Human; Hypoxia; Immune response; Immunohistochemistry; Infant; Infection; Inflammation; Inflammatory; Injury; Interruption; Intervention; Intracranial Hemorrhages; Learning; Life; Lipopolysaccharides; Magnetic Resonance Imaging; Measurement; Modeling; Motor; Mus; Mustela putorius furo; Neonatal; Neonatal Brain Injury; Neurodevelopmental Impairment; Neurons; Neurosciences; Oryctolagus cuniculus; Outcome; Pathologic; Pattern; Perinatal; Perinatology; Physiological; Pregnancy; Premature Infant; Preterm brain injury; Rattus; Reproduction; Risk; Rodent; Rodent Model; Sheep; Staging; Survivors; Therapeutic; Third Pregnancy Trimester; Tissues; Translating; Translations; Vaccines; behavior test; cost; cytokine; fetal; gray matter; human disease; improved; instrumentation; interest; migration; mortality; neonate; neurodevelopment; neurogenesis; neuroprotection; nonhuman primate; novel; novel therapeutics; postnatal; preclinical trial; premature; prenatal; species difference; success; tool; white matter; white matter injury

 DESCRIPTION (provided by applicant): The goal of this proposal is to develop a novel small animal model of neonatal brain injury to describe mechanisms of preterm brain injury and neuroprotection that can translate effectively to humans. Up to 50% of infants born extremely preterm develop poor outcomes involving long-term neurodevelopmental impairments affecting cognition and learning, or motor problems such as cerebral palsy. Poor outcomes arise because the preterm brain is vulnerable both to direct injury (by events such as intracerebral hemorrhage, infection and/or hypoxia), or indirect injury due to disruption of normal development. Developing white matter is particularly vulnerable to inflammation and hypoxia during the third trimester, and white matter injury is prevalent in preterm survivors. The combination of neonatal brain injury and disruption of brain development is called encephalopathy of prematurity. Rodents are the most common species used to model neonatal brain injury. But one shortcoming of using rodents is that they have a much lower proportion of white matter when compared to humans (12.5% vs. 50% white/gray). This species difference in the proportion of white matter has limited translation of rodent neuroprotective strategies to human neonates. Neonatal ferrets (Mustela putorius furo) provide a more promising opportunity to study brain injury and development relevant to preterm humans for a number of reasons. In comparison to rodents, ferrets have a more favorable white to gray matter ratio, greater cortical gyrification and, they undergo prolonged postnatal brain development so postnatal interventions may be performed at relevant stages of brain development. On postnatal day (P) 9, ferret brain development correlates well with human brain development at 25 weeks of gestation, while P21 ferret brains correspond to term gestation in human brains. We propose to create a pathophysiologically relevant ferret model of preterm brain injury that will recreate injuries associated with encephalopathy of prematurity and enable description of the underlying neuropathologic mechanisms and discovery of translatable neuroprotective strategies. Our Specific Aims are to: 1) use the bacterial endotoxin lipopolysaccharide (LPS) to create and characterize acute and chronic inflammation in P9 ferret brain; 2) evaluate the effects of hypoxia and hypoxia-ischemia on ferret brain growth and development; and 3) identify the interaction effects of acute and chronic LPS-induced inflammation with hypoxia and hypoxia-ischemia in neonatal ferret brain. Inflammatory cytokines, magnetic resonance imaging (MRI) and immunohistochemistry (IHC) will be used to assess inflammation, injury, growth and development. We are confident that completion of these aims will produce a better understanding of the pathologic mechanisms underlying neonatal brain injury, and improve our capacity to validate new therapies for human neuroprotection.



项目成果

Is the ferret a suitable species for studying perinatal brain injury?

• DOI: 10.1016/j.ijdevneu.2015.06.005
• 发表时间: 2015-10-01
• 期刊: INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
• 影响因子: 1.8
• 作者: Empie, Kristen;Rangarajan, Vijayeta;Juul, Sandra E.
• 通讯作者: Juul, Sandra E.

A Ferret Model of Encephalopathy of Prematurity.

早产儿脑病的雪貂模型。

• DOI: 10.1159/000498968
• 发表时间: 2018
• 期刊: Developmental neuroscience
• 影响因子: 2.9
• 作者: Wood,Thomas;Moralejo,Daniel;Corry,Kylie;Snyder,JessicaM;Traudt,Christopher;Curtis,Chad;Nance,Elizabeth;Parikh,Pratik;Juul,SandraE
• 通讯作者: Juul,SandraE

A Ferret Model of Inflammation-sensitized Late Preterm Hypoxic-ischemic Brain Injury.

炎症敏感的晚期早产缺氧缺血性脑损伤的雪貂模型。

• DOI: 10.3791/60131
• 发表时间: 2019
• 期刊: Journal of visualized experiments : JoVE
• 作者: Wood,Thomas;Moralejo,Daniel;Corry,Kylie;Fisher,Cole;Snyder,JessicaM;Acuna,Vivienne;Holden-Hunt,Alair;Virk,Simar;White,Olivia;Law,Janessa;Parikh,Pratik;Juul,SandraE
• 通讯作者: Juul,SandraE