Consequences of intraventricular hemorrhage in a rabbit pup model.
Consequences of intraventricular hemorrhage in a rabbit pup model.
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DOI：
10.1161/strokeaha.109.549212
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发表时间：
2009-10
期刊：
影响因子：
8.3
通讯作者：
Ballabh P
中科院分区：
文献类型：
--
作者：
Chua CO;Chahboune H;Braun A;Dummula K;Chua CE;Yu J;Ungvari Z;Sherbany AA;Hyder F;Ballabh P
Intraventricular hemorrhage (IVH) is a common complication of prematurity that results in neurologic sequelae including cerebral palsy, post-hemorrhagic hydrocephalus and cognitive deficits. Despite this, there is no standardized animal model exhibiting neurological consequences of IVH in prematurely delivered animals. We asked whether induction of moderate-to-severe IVH in premature rabbit pups would produce long-term sequelae of cerebral palsy, posthemorrhagic hydrocephalus, reduced myelination and gliosis. The premature rabbit pups, delivered by C-section, were treated with intraperitoneal glycerol at 2h postnatal age to induce IVH. The development of IVH was diagnosed by head ultrasound at 24h age. Neuro-behavioral, histological and ultrastructural evaluation and diffusion tensor imaging (DTI) studies were performed at 2-week age. While 25% IVH pups developed motor impairment with hypertonia and 42% developed post-hemorrhagic hydrocephalus, pups without IVH (non-IVH) were unremarkable. Immunolabeling revealed reduced myelination in the white matter of IVH pups compared to saline- and glycerol-treated non-IVH controls. Reduced myelination was confirmed by Western blot analysis. There was evidence of gliosis in IVH pups. Ultrastructural studies in IVH pups showed that myelinated and unmyelinated fibers were relatively preserved except for focal axonal injury. DTI showed reduction in fractional anisotropy and white matter volume confirming white matter injury in IVH pups. The rabbit pups with IVH displayed post-hemorrhagic hydrocephalus, gliosis, reduced myelination and motor deficits, like humans. The study highlights an instructive animal model of the neurologic consequences of IVH, which can be used to evaluate strategies in the prevention and treatment of post-hemorrhagic complications.
