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在一种新的类脑回动物急性脑出血模型中,通过自动化图像处理进行病灶和病灶周围组织特征描述。

Lesional and perilesional tissue characterization by automated image processing in a novel gyrencephalic animal model of peracute intracerebral hemorrhage.

机构信息

Department of Translational Medicine and Cell Technology, Fraunhofer Research Institution for Marine Biotechnology and Cell Technology, Lübeck, Germany.

Institute for Medical and Marine Biotechnology, University of Lübeck, Lübeck, Germany.

出版信息

J Cereb Blood Flow Metab. 2019 Dec;39(12):2521-2535. doi: 10.1177/0271678X18802119. Epub 2018 Sep 21.

DOI:10.1177/0271678X18802119
PMID:30239258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6893983/
Abstract

Intracerebral hemorrhage (ICH) is an important stroke subtype, but preclinical research is limited by a lack of translational animal models. Large animal models are useful to comparatively investigate key pathophysiological parameters in human ICH. To (i) establish an acute model of moderate ICH in adult sheep and (ii) an advanced neuroimage processing pipeline for automatic brain tissue and hemorrhagic lesion determination; 14 adult sheep were assigned for stereotactically induced ICH into cerebral white matter under physiological monitoring. Six hours after ICH neuroimaging using 1.5T MRI including structural as well as perfusion and diffusion, weighted imaging was performed before scarification and subsequent neuropathological investigation including immunohistological staining. Controlled, stereotactic application of autologous blood caused a space-occupying intracerebral hematoma of moderate severity, predominantly affecting white matter at 5 h post-injection. Neuroimage post-processing including lesion probability maps enabled automatic quantification of structural alterations including perilesional diffusion and perfusion restrictions. Neuropathological and immunohistological investigation confirmed perilesional vacuolation, axonal damage, and perivascular blood as seen after human ICH. The model and imaging platform reflects key aspects of human ICH and enables future translational research on hematoma expansion/evacuation, white matter changes, hematoma evacuation, and other aspects.

摘要

脑出血(ICH)是一种重要的中风亚型,但临床前研究受到缺乏转化动物模型的限制。大型动物模型可用于比较研究人类 ICH 的关键病理生理参数。(i)建立成年绵羊急性中度 ICH 模型,(ii)建立先进的神经影像处理管道,用于自动确定脑组织和出血病变;14 只成年绵羊在生理监测下接受立体定向诱导的大脑白质 ICH。ICH 后 6 小时,使用 1.5T MRI 进行神经影像学检查,包括结构以及灌注和扩散加权成像,在进行尸检和随后的神经病理学研究(包括免疫组织化学染色)之前进行。自体血的控制性、立体定向应用导致了中等严重程度的占位性颅内血肿,主要影响注射后 5 小时的白质。包括病变概率图在内的神经影像后处理能够自动量化包括病变周围扩散和灌注受限在内的结构改变。神经病理学和免疫组织化学研究证实了人类 ICH 后所见的病变周围空泡化、轴突损伤和血管周围血液。该模型和成像平台反映了人类 ICH 的关键方面,并能够进行血肿扩大/清除、白质变化、血肿清除等方面的未来转化研究。

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本文引用的文献

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Basic and Translational Research in Intracerebral Hemorrhage: Limitations, Priorities, and Recommendations.脑出血的基础与转化研究:局限性、优先事项及建议
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Concise Review: Increasing the Validity of Cerebrovascular Disease Models and Experimental Methods for Translational Stem Cell Research.简明综述:提高转化干细胞研究中脑血管病模型和实验方法的有效性。
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Peri-Hemorrhagic Edema and Secondary Hematoma Expansion after Intracerebral Hemorrhage: From Benchwork to Practical Aspects.脑出血后出血周围水肿及继发性血肿扩大:从基础研究到实际应用
Front Neurol. 2017 Jan 19;8:4. doi: 10.3389/fneur.2017.00004. eCollection 2017.
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Translational models for vascular cognitive impairment: a review including larger species.血管性认知障碍的转化模型:包括大型物种的综述
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von Willebrand factor contributes to poor outcome in a mouse model of intracerebral haemorrhage.血管性血友病因子导致脑出血小鼠模型预后不良。
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