Mouse models of periventricular leukomalacia.
Mouse models of periventricular leukomalacia.
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DOI：
10.3791/1951
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发表时间：
2010-05-18
期刊：
影响因子：
--
通讯作者：
Deng, Wenbin
中科院分区：
文献类型：
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作者：
Shen, Yan;Plane, Jennifer M;Deng, Wenbin
我们描述了一种建立小鼠脑室周围白质软化（PVL）模型的方案。PVL是早产儿脑损伤的主要形式，也是脑瘫最常见的前兆。PVL以心室周围白质损伤和突出的少突胶质损伤为特征。缺氧/缺血伴或不伴全身性感染/炎症是PVL的主要原因。我们使用P6小鼠，通过单侧颈动脉结扎诱导缺氧/缺血（伴或不伴全身性感染/炎症），然后暴露于缺氧（伴或不伴内毒素脂多糖（LPS）注射），建立新生儿脑损伤模型。髓鞘碱性蛋白（MBP）或O1的免疫组化和电镜检查显示，脑白质中髓鞘明显丢失，海马和丘脑受到额外损伤。PVL小鼠模型的建立将极大地促进利用现有转基因小鼠品系研究疾病发病机制，以相对高通量的方式进行药物试验以确定候选治疗剂，以及利用免疫缺陷小鼠品系进行干细胞移植试验。
We describe a protocol for establishing mouse models of periventricular leukomalacia (PVL). PVL is the predominant form of brain injury in premature infants and the most common antecedent of cerebral palsy. PVL is characterized by periventricular white matter damage with prominent oligodendroglial injury. Hypoxia/ischemia with or without systemic infection/inflammation are the primary causes of PVL. We use P6 mice to create models of neonatal brain injury by the induction of hypoxia/ischemia with or without systemic infection/inflammation with unilateral carotid ligation followed by exposure to hypoxia with or without injection of the endotoxin lipopolysaccharide (LPS). Immunohistochemistry of myelin basic protein (MBP) or O1 and electron microscopic examination show prominent myelin loss in cerebral white matter with additional damage to the hippocampus and thalamus. Establishment of mouse models of PVL will greatly facilitate the study of disease pathogenesis using available transgenic mouse strains, conduction of drug trials in a relatively high throughput manner to identify candidate therapeutic agents, and testing of stem cell transplantation using immunodeficiency mouse strains.