Chronic Hydrocephalus and Perihematomal Tissue Injury Developed in a Rat Model of Intracerebral Hemorrhage with Ventricular Extension
Chronic Hydrocephalus and Perihematomal Tissue Injury Developed in a Rat Model of Intracerebral Hemorrhage with Ventricular Extension
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DOI：
10.1007/s12975-014-0367-5
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发表时间：
2015-04-01
影响因子：
6.9
通讯作者：
Chen, Zhi
中科院分区：
文献类型：
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作者：
Chen, Qianwei;Zhang, Jianbo;Chen, Zhi
原发性自发性脑内出血（ICH）合并继发性脑室内出血（IVH）是一个重要的临床问题，但人们对其了解甚少。脑室内出血和脑积水是脑内出血不良预后的独立预测因素。因此，本研究的目的是建立一种伴有脑室扩展的脑内出血大鼠模型，并研究出血后慢性脑积水的发生以及血肿周围组织损伤情况。基于我们之前的脑室内出血大鼠模型，我们调整了注射坐标，将200微升自体血立体定向注入右侧纹状体（坐标：前囟后0.2毫米、外侧2.2毫米、深度5.0毫米）。在注入后24小时，大鼠产生可重复的血肿和脑室扩张，这与人脑内伴有脑室扩展的脑内出血情况非常相似。在急性期对血肿后果和血肿周围组织损伤进行了评估。在4周时，通过磁共振成像测量脑室扩张、脑组织丢失、海马体积和皮质厚度，并使用莫里斯水迷宫试验评估神经认知功能。随着血液注入，动物在急性期表现出脑水肿、血脑屏障破坏以及明显的血肿周围组织损伤。在4周时，T2图像显示明显的脑积水和组织丢失，莫里斯水迷宫试验显示神经认知功能缺陷。目前这种伴有脑室扩展的脑内出血大鼠模型兼具脑内出血和脑室内出血大鼠模型的特点，可用于加深我们对出血后慢性脑积水和血肿周围组织损伤的病理生理学理解。
Primary spontaneous intracerebral hemorrhage (ICH) with secondary intraventricular hemorrhage (IVH) is an important clinical problem of which little is known. IVH and hydrocephalus are independent predictors of poor outcome in ICH. The aims of this study were, therefore, to establish a rat model of ICH with ventricular extension and investigate the occurrence of post-hemorrhagic chronic hydrocephalus and perihematomal tissue injury. Based on our previous rat model of IVH, we adjusted the injection coordinates and 200 mu l autologous blood was stereotaxically infused into the right striatum (coordinates: 0.2 mm posterior, 2.2 mm lateral, and 5.0 mm depth to the bregma). At 24 h post-infusion, the rats produced reproducible hematoma and ventricle expansion, which closely mimics the ICH with ventricular extension in humans. Hematoma consequences and perihematomal tissue injury were evaluated on the acute phase. At 4 weeks, ventricular dilatation, brain tissue loss, hippocampus volume, and cortical thickness were measured with magnetic resonance imaging and neurocognitive function was assessed using the Morris water maze test. With blood infusion, the animals demonstrated brain edema, blood-brain barrier breakdown, and marked perihematomal tissue injury on the acute phase. At 4 weeks, the T2 images showed remarkable hydrocephalus and tissue loss, and the Morris water maze test revealed neurocognitive deficits. The present ICH with the ventricular extension rat model features characteristics of both ICH and IVH rat models, which could be used for extending our pathophysiological understanding of post-hemorrhagic chronic hydrocephalus and perihematomal tissue damage.