Prior research on 3-week hydrocephalic rats showed that behavioral deficits and white matter damage could be reduced by treatment with Ca2+ 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.
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机译：对3周脑积水大鼠的先前研究表明，通过使用Ca2 +通道阻滞剂尼莫地平治疗可以减少行为缺陷和白质损害。我们假设尼莫地平治疗对高岭土诱导的脑积水的年轻雪貂也将有益。在14周龄时诱发脑积水，并用媒介物，低剂量尼莫地平（3.2？mg / kg /天）或高剂量尼莫地平（16？mg / kg /天）对动物进行治疗，从38周至2周。 52天的年龄。脑积水脑积水发展为进行性脑室肥大，行为改变，在某些情况下还发生皮层失明。尼莫地平没有改善这些改变。组织学检查显示，与非脑积水对照组相比，脑室周围白质损伤，call体变薄，轴突损伤，星形胶质细胞反应性改变和细胞增殖受到抑制。尼莫地平治疗对上述任何病理改变均无益处;尽管脑室较大，但只有低剂量尼莫地平治疗与胶质纤维酸性蛋白含量正常化有关。我们得出的结论是，年轻的脑积水雪貂遇到行为障碍和结构性脑损伤，而尼莫地平间歇治疗并不能持续改善这种情况。在进一步的临床前研究中应考虑持续分娩。
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