Department of Human Anatomy & Cell Science, University of Manitoba, Canada; Manitoba Institute of Child Health, Canada.
Exp Neurol. 2013 Oct;248:112-28. doi: 10.1016/j.expneurol.2013.06.004. Epub 2013 Jun 12.
Hydrocephalus is a neurological condition characterized by altered cerebrospinal fluid (CSF) flow with enlargement of ventricular cavities in the brain. A reliable model of hydrocephalus in gyrencephalic mammals is necessary to test preclinical hypotheses. Our objective was to characterize the behavioral, structural, and histological changes in juvenile ferrets following induction of hydrocephalus. Fourteen-day old ferrets were given an injection of kaolin (aluminum silicate) into the cisterna magna. Two days later and repeated weekly until 56 days of age, magnetic resonance (MR) imaging was used to assess ventricle size. Behavior was examined thrice weekly. Compared to age-matched saline-injected controls, severely hydrocephalic ferrets weighed significantly less, their postures were impaired, and they were hyperactive prior to extreme debilitation. They developed significant ventriculomegaly and displayed white matter destruction. Reactive astroglia and microglia detected by glial fibrillary acidic protein (GFAP) and Iba-1 immunostaining were apparent in white matter, cortex, and hippocampus. There was a hydrocephalus-related increase in activated caspase 3 labeling of apoptotic cells (7.0 vs. 15.5%) and a reduction in Ki67 labeling of proliferating cells (23.3 vs. 5.9%) in the subventricular zone (SVZ). Reduced Olig2 immunolabeling suggests a depletion of glial precursors. GFAP content was elevated. Myelin basic protein (MBP) quantitation and myelin biochemical enzyme activity showed early maturational increases. Where white matter was not destroyed, the remaining axons developed myelin similar to the controls. In conclusion, the hydrocephalus-induced periventricular disturbances may involve developmental impairments in cell proliferation and glial precursor cell populations. The ferret should prove useful for testing hypotheses about white matter damage and protection in the immature hydrocephalic brain.
脑积水是一种以脑室内腔扩大为特征的神经学疾病，通常伴随着脑脊液（CSF）流动的改变。在具有脑回结构的哺乳动物中建立可靠的脑积水模型，对于检验临床前假说至关重要。本研究的目的是描述幼龄雪貂脑积水模型中行为学、结构和组织学的变化。14 日龄雪貂通过枕大池向脑室内注入高岭土（硅酸铝）。两天后，每周重复注射一次，直到 56 日龄，通过磁共振成像（MR）评估脑室大小。每周检测 3 次行为学。与年龄匹配的生理盐水对照组相比，重度脑积水雪貂的体重明显减轻，姿势异常，在极度虚弱之前表现出过度活跃。它们出现了明显的脑室扩大和白质破坏。胶质纤维酸性蛋白（GFAP）和 Iba-1 免疫染色检测到的反应性星形胶质细胞和小胶质细胞在白质、皮质和海马中均有明显表达。脑室周围区（SVZ）中，激活的 caspase-3 标记的凋亡细胞数量（7.0%对 15.5%）和增殖细胞 Ki67 标记数量（23.3%对 5.9%）均有与脑积水相关的增加。少突胶质细胞标记物 Olig2 的减少提示少突胶质前体细胞耗竭。GFAP 含量升高。髓鞘碱性蛋白（MBP）定量和髓鞘生化酶活性显示早期成熟度增加。在未被破坏的白质中，剩余的轴突形成了与对照组相似的髓鞘。总之，脑室周围的脑积水诱导改变可能涉及细胞增殖和少突胶质前体细胞群体的发育障碍。雪貂模型应有助于检验在未成熟脑积水大脑中白质损伤和保护的假说。
