Using Zebrafish Larvae to Study the Pathological Consequences of Hemorrhagic Stroke
Using Zebrafish Larvae to Study the Pathological Consequences of Hemorrhagic Stroke
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DOI：
10.3791/59716
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发表时间：
2019-06-01
影响因子：
1.2
通讯作者：
Kasher, Paul R.
中科院分区：
文献类型：
--
作者：
Crilly, Siobhan;Njegic, Alexandra;Kasher, Paul R.
尽管脑出血是全球死亡率高的最严重的脑卒中亚型，但脑出血患者尚无特异性治疗方法。对脑出血进行临床前建模已被证明是困难的，目前的啮齿动物模型很难概括人类脑出血的自发性。因此，迫切需要替代的临床前方法来研究脑出血的疾病机制和潜在的药物发现。斑马鱼的使用代表了一种越来越受欢迎的转化研究方法，主要是因为它们比哺乳动物疾病模型具有许多优势，包括多产的繁殖率和允许实时成像的幼虫透明度。其他研究小组已经确定，斑马鱼幼体在脑血管发育的遗传或化学破坏后，可表现出自发性脑出血。这种方法的目的是利用这些模型来研究脑出血的病理后果，在临床前脑出血研究的背景下。通过实时成像和运动分析，可以评估和量化脑出血后的脑损伤、神经炎症和运动功能。这项研究表明，人类脑出血的关键病理后果在斑马鱼幼虫中是保守的，突出了这种模式生物作为脑出血临床前研究的有价值的体内系统。该方法的目的是使临床前卒中社区能够采用斑马鱼幼虫模型作为啮齿动物的替代补充模型系统。
Despite being the most severe subtype of stroke with high global mortality, there is no specific treatment for patients with intracerebral hemorrhage (ICH). Modelling ICH pre-clinically has proven difficult, and current rodent models poorly recapitulate the spontaneous nature of human ICH. Therefore, there is an urgent requirement for alternative pre-clinical methodologies for study of disease mechanisms in ICH and for potential drug discovery.The use of zebrafish represents an increasingly popular approach for translational research, primarily due to a number of advantages they possess over mammalian models of disease, including prolific reproduction rates and larval transparency allowing for live imaging. Other groups have established that zebrafish larvae can exhibit spontaneous ICH following genetic or chemical disruption of cerebrovascular development. The aim of this methodology is to utilize such models to study the pathological consequences of brain hemorrhage, in the context of preclinical ICH research. By using live imaging and motility assays, brain damage, neuroinflammation and locomotor function following ICH can be assessed and quantified.This study shows that key pathological consequences of brain hemorrhage in humans are conserved in zebrafish larvae highlighting the model organism as a valuable in vivo system for pre-clinical investigation of ICH. The aim of this methodology is to enable the pre-clinical stroke community to employ the zebrafish larval model as an alternative complementary model system to rodents.