Characterization of Acute Brain Injuries and Neurobehavioral Profiles in a Rabbit Model of Germinal Matrix Hemorrhage
Characterization of Acute Brain Injuries and Neurobehavioral Profiles in a Rabbit Model of Germinal Matrix Hemorrhage
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DOI：
10.1161/strokeaha.107.510883
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发表时间：
2008-12-01
期刊：
影响因子：
8.3
通讯作者：
Ballabh, Praveen
中科院分区：
文献类型：
--
作者：
Georgiadis, Paraskevi;Xu, Hongmin;Ballabh, Praveen
背景和目的-生发基质出血-脑室出血(GMH-IVH)是早产儿最常见的神经系统问题，具有巨大的经济和社会影响。尽管如此，目前还没有描述急性脑损伤的标准化的IVH动物模型。方法：我们通过剖腹产的方式早产29天的幼兔，在出生后3小时给幼鼠注射甘油诱导IVH，并评估大脑损伤的证据。结果-大约80%的幼鼠发生了严重的IVH。我们发现IVH幼鼠的脑室周围(脑室周围区)有更多的中性粒细胞和小胶质细胞的渗透。我们注意到IVH幼鼠脑室周围区的细胞凋亡和神经元变性比新皮质多，但在对照组中没有。β-淀粉样前体蛋白和神经丝免疫标记显示轴突损伤。神经行为测试表明，与没有IVH的幼鼠相比，患有IVH的幼崽更不稳定，倾斜行走的能力更差。在甘油处理的幼鼠中没有急性全身毒性的证据。对早产儿尸检材料的评估显示，在有IVH的病例中，脑室周围区有类似的细胞凋亡和细胞浸润的证据，但在没有IVH的病例中没有，这表明该模型具有临床意义。结论-本研究提供了一个有指导意义的IVH动物模型，提供了急性脑损伤的证据，可用于评估预防IVH和急性出血后并发症的策略。(笔划。2008；39：3378-3388。)
Background and Purpose-Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common neurological problem of premature infants and has enormous financial and social impact. Despite this, there is no standardized animal model of IVH depicting acute brain injuries.Methods-We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries.Results-About 80% of glycerol-treated pups developed gross IVH. We found greater neutrophil and microglia infiltration around the ventricles (periventricular zone) in pups with IVH than in controls. We noted more apoptosis and neuronal degeneration in the periventricular zone than in the neocortex in pups with IVH, but not in controls. There was evidence of axonal damage revealed by beta-amyloid precursor protein and neurofilament immunolabeling. Neurobehavioral testing showed that pups with IVH were more wobbly with lesser capability to walk on inclination than pups without IVH. There was no evidence of acute systemic toxicity in the glycerol-treated pups. An evaluation of autopsy materials from premature infants revealed similar evidence of apoptosis and cellular infiltration in the periventricular zone in cases with IVH, but not in cases without IVH-suggesting clinical relevance of the model.Conclusion-The study provides an instructive animal model of IVH with evidence of acute brain injuries that can be used to evaluate strategies in prevention of IVH and acute posthemorrhagic complications. (Stroke. 2008; 39: 3378-3388.)