Tao Chuanyuan, Zhang Ruzhi, Hu Xin, Song Li, Wang Chunhua, Gao Fabao, You Chao
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
J Stroke Cerebrovasc Dis. 2016 May;25(5):1102-1109. doi: 10.1016/j.jstrokecerebrovasdis.2016.01.025. Epub 2016 Feb 15.
Primary brainstem hemorrhage (BSH) has the highest mortality and morbidity as a subtype of intracerebral hemorrhage. A major limitation of BSH research is the lack of a corresponding animal model. The purpose of this study was to establish a novel rat model of BSH and to characterize the resulting brain injury, especially focusing on white matter injury.
BSH was produced by stereotactically injecting autologous whole blood into the pons. Time course of hematoma resolution was observed by 7-T magnetic resonance imaging. White matter injury was evaluated in detail by multiple parameters including diffuse tensor imaging (DTI), demyelination, axonal injury, oligodendrocyte degeneration, and oligodendrocyte precursor cell proliferation. Brain water content and neurobehavior were also evaluated.
Blood infusion (30 µL) led to a stable, reproducible hematoma in the right basotegmental pons. The hematoma absorption started, became obvious, and was nearly completed at 7, 14, and 30 days, respectively. Hematoma caused obvious brain edema at 3 days. White mater injury was observed pathologically, which was in line with decreased fractional anisotropy (FA) in DTI in the pons. FA reduction was also noticed in the cerebral peduncle and medulla. Behavioral abnormality persisted for at least 14 days and neurofunction was recovered within 1 month.
This novel model can produce a stable hematoma resulting in brain edema, white matter injury, and neurofunctional deficits, which could be useful for future investigation of pathophysiological mechanisms and new treatment evaluation after BSH.
原发性脑干出血（BSH）作为脑出血的一种亚型，具有最高的死亡率和发病率。BSH研究的一个主要局限性是缺乏相应的动物模型。本研究的目的是建立一种新型大鼠BSH模型，并对由此产生的脑损伤进行特征描述，尤其关注白质损伤。
通过立体定向将自体全血注入脑桥来制造BSH。通过7-T磁共振成像观察血肿吸收的时间进程。通过包括弥散张量成像（DTI）、脱髓鞘、轴突损伤、少突胶质细胞变性和少突胶质前体细胞增殖在内的多个参数详细评估白质损伤。还评估了脑含水量和神经行为。
注入30μL血液导致右基底被盖脑桥出现稳定且可重复的血肿。血肿吸收分别在7天、14天和30天开始、变得明显并几乎完成。血肿在3天时导致明显的脑水肿。在病理上观察到白质损伤，这与脑桥DTI中各向异性分数（FA）降低一致。在大脑脚和延髓也观察到FA降低。行为异常持续至少14天，神经功能在1个月内恢复。
这种新型模型可产生稳定的血肿，导致脑水肿、白质损伤和神经功能缺损，这可能有助于未来对BSH后病理生理机制和新治疗评估的研究。
