Department of Pathology, University of Manitoba, 401-727 McDermot Avenue, Winnipeg, MB, R3E 3P5, Canada.
Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada.
Fluids Barriers CNS. 2018 May 3;15(1):14. doi: 10.1186/s12987-018-0099-0.
Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca channel blocker nimodipine. We hypothesized that treatment with nimodipine would be also beneficial to young ferrets with kaolin-induced hydrocephalus. Hydrocephalus was induced at 14 days of age and animals were treated either with vehicle, low dose nimodipine (3.2 mg/kg/day), or high dose nimodipine (16 mg/kg/day) for 2 weeks from 38 to 52 days age. Hydrocephalic ferrets developed progressive ventriculomegaly, behavioral changes, and in some cases cortical blindness. These changes were not ameliorated by nimodipine. Histological examination showed damage in periventricular white matter, corpus callosum thinning, axonal damage, reactive astroglial changes, and suppressed cell proliferation compared to non-hydrocephalic controls. Treatment with nimodipine was not beneficial for any of the pathological changes mentioned above; only low dose nimodipine treatment was associated with normalized content of glial fibrillary acidic protein, despite larger ventricles. We conclude that young hydrocephalic ferrets experience behavioral impairments and structural brain damage that are not consistently improved by intermittent nimodipine treatment. Continuous delivery should be considered in further preclinical studies.
先前关于 3 周脑积水大鼠的研究表明，钙通道阻滞剂尼莫地平治疗可减轻行为缺陷和白质损伤。我们假设尼莫地平治疗对高岭土诱导的脑积水幼貂也有益处。脑积水在 14 日龄时诱导，动物在 38 至 52 日龄期间用载体、低剂量尼莫地平（3.2mg/kg/天）或高剂量尼莫地平（16mg/kg/天）治疗 2 周。脑积水貂出现进行性脑室扩大、行为改变，在某些情况下出现皮质盲。尼莫地平不能改善这些变化。组织学检查显示，与非脑积水对照相比，脑室周围白质、胼胝体变薄、轴突损伤、反应性星形胶质细胞变化和细胞增殖受到抑制。尼莫地平治疗对上述任何病理变化都没有益处；只有低剂量尼莫地平治疗与神经胶质纤维酸性蛋白含量正常化有关，尽管脑室较大。我们的结论是，年轻的脑积水貂经历行为障碍和结构脑损伤，间歇性尼莫地平治疗并不能持续改善这些损伤。在进一步的临床前研究中应考虑持续给药。
