内皮素-1 诱导成年斑马鱼全脑缺血：一种具有新型中风研究实体的模型。

Endothelin-1 induced global ischaemia in adult zebrafish: A model with novel entity of stroke research.

机构信息

Department of Pharmacology, Nirma University, Ahmadabad, Gujarat, India.

出版信息

J Chem Neuroanat. 2021 Dec;118:102025. doi: 10.1016/j.jchemneu.2021.102025. Epub 2021 Sep 11.

DOI:10.1016/j.jchemneu.2021.102025

PMID:34520802

Abstract

BACKGROUND

Stroke is a leading cause of death in the general population, and it occurs three times more frequently in diabetic patients, necessitating extensive research into new therapeutics. The reproducibility, similarity, and technical limitations of current animal models are limited.

METHODS

We developed a stroke induction model using pink zebra-Danio-rerio. Diabetes was induced in zebrafish by giving them D-glucose (111 mM) for 14 days, and those with blood glucose levels higher than 100 mg/dl were included in the study. In Zebrafish, an experimental stroke was induced by a single oral administration of Endothelin-1 (ET-1, 3µl/gm). Swimming, behavioural patterns, and cognitive performance were all recorded and analysed using UMA Tracker. The brains were removed for histopathological analysis.

RESULTS

In both the normal and diabetic groups, ET-1 administration resulted in a statistically significant change in swimming pattern and movements. Furthermore, changes in swimming pattern and recovery time were statistically significant in the diabetic ET-1 treatment group. In the neurocognitive assessment paradigm, the behavioural study of ET-1 treated groups revealed a disturbed cognitive profile and locomotor coordination, with an increase in the number of errors and a decrease in total distance travelled. Histopathological analysis of ET-1 treated groups revealed cortical lesions, shrunken neuronal cells, and thrombocytes in spheroid form with disturbed normal architecture of brain tissue when compared to normal control groups in tectum opticum and telencephalon. In terms of stability, reproducibility, and genetic similarity to human stroke, the current experimental model outperforms other available rodent stroke models.

CONCLUSION

The ET-1 induced experimental zebrafish stroke model opens up new avenues for diabetes-related stroke research due to its novelty, reproducibility, and ability to overcome technical errors found in other recent models.

摘要

背景

中风是普通人群中主要的致死原因，糖尿病患者的中风发病率高出三倍，因此需要对新的治疗方法进行广泛研究。目前动物模型的可重复性、相似性和技术局限性有限。

方法

我们使用粉色斑马鱼- Danio-rerio 开发了一种中风诱导模型。通过给斑马鱼喂食 D-葡萄糖（111mM）14 天来诱导糖尿病，将血糖水平高于 100mg/dl 的斑马鱼纳入研究。在斑马鱼中，通过单次口服内皮素-1（ET-1，3µl/gm）诱导实验性中风。使用 UMA Tracker 记录和分析游泳、行为模式和认知表现。取出大脑进行组织病理学分析。

结果

在正常组和糖尿病组中，ET-1 给药均导致游泳模式和运动发生统计学显著变化。此外，糖尿病 ET-1 治疗组的游泳模式和恢复时间变化具有统计学意义。在神经认知评估范式中，ET-1 处理组的行为研究显示认知功能障碍和运动协调紊乱，错误次数增加，总距离减少。与正常对照组相比，ET-1 处理组的组织病理学分析显示皮质病变、神经元细胞缩小和呈球形的血小板，脑组织的正常结构受到干扰。在稳定性、可重复性和与人类中风的遗传相似性方面，目前的实验模型优于其他现有的啮齿动物中风模型。