Khan Osaama H, Enno Terry L, Del Bigio Marc R
Department of Pathology, University of Manitoba, Winnipeg, Canada Manitoba Institute for Child Health, Winnipeg, Canada.
Exp Neurol. 2006 Aug;200(2):311-20. doi: 10.1016/j.expneurol.2006.02.113. Epub 2006 Apr 19.
Neonatal and congenital hydrocephalus are common problems in humans. Hydrocephalus was induced in 1-day-old rats by injection of kaolin into the cisterna magna. At 7 and 21 days, magnetic resonance (MR) imaging was used to assess ventricle size, then brains were subjected to histopathological and biochemical analyses. Hydrocephalic pups did not exhibit delays in righting or negative geotaxis reflexes during the first week. At 7 days, there was variable ventricular enlargement with periventricular white matter edema, axon damage, reactive astrogliosis, and accumulation of macrophages in severe but not mild hydrocephalus. Cellular proliferation in the subependymal zone was significantly reduced. The cortical subplate neuron layer was disrupted. In rats allowed to survive to 21 days, weight was significantly lower in severely hydrocephalic rats. They also exhibited impaired memory in the Morris water maze test. Despite abnormal posture, there was minimal quantitative impairment of walking ability on a rotating cylinder. At 21 days, histological studies showed reduced corpus callosum thickness, fewer mature oligodendrocytes, damaged axons, and astroglial/microglial reaction. Reduced myelin basic protein, increased glial fibrillary acidic protein, and stable synaptophysin content were demonstrated by immunochemical methods. In conclusion, impairment in cognition and motor skills corresponds to ventricular enlargement and white matter destruction. Quantitative measures of weight, memory, ventricle size, and myelin, and glial proteins in this neonatal model of hydrocephalus will be useful tools for assessment of experimental therapeutic interventions.
新生儿和先天性脑积水是人类常见的问题。通过向1日龄大鼠的大池内注射高岭土诱导脑积水。在第7天和第21天，使用磁共振（MR）成像评估脑室大小，然后对大脑进行组织病理学和生化分析。脑积水幼崽在第一周内未表现出翻正或负趋地性反射延迟。在第7天，存在不同程度的脑室扩大，伴有脑室周围白质水肿、轴突损伤、反应性星形胶质细胞增生，并且在重度而非轻度脑积水中有巨噬细胞积聚。室管膜下区的细胞增殖显著减少。皮质下板神经元层被破坏。在存活至21天的大鼠中，重度脑积水大鼠的体重显著降低。它们在莫里斯水迷宫试验中也表现出记忆受损。尽管姿势异常，但在旋转圆柱体上行走能力的定量损伤最小。在第21天，组织学研究显示胼胝体厚度减小、成熟少突胶质细胞减少、轴突损伤以及星形胶质细胞/小胶质细胞反应。免疫化学方法显示髓鞘碱性蛋白减少、胶质纤维酸性蛋白增加以及突触素含量稳定。总之，认知和运动技能的损害与脑室扩大和白质破坏相对应。在这个新生儿脑积水模型中，体重、记忆、脑室大小以及髓鞘和胶质蛋白的定量测量将是评估实验性治疗干预的有用工具。
