Journal of Chemical Neuroanatomy ( IF 2.7 ) Pub Date : 2021-09-11 , DOI: 10.1016/j.jchemneu.2021.102025 Vishal Chavda 1 , Snehal Patel 1 , Badrah S Alghamdi 2 , Ghulam Md Ashraf 3
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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.
中文翻译：
内皮素-1诱导成年斑马鱼全身缺血：中风研究新实体模型
背景
中风是普通人群的主要死亡原因，在糖尿病患者中的发生频率是其三倍，因此需要对新疗法进行广泛研究。当前动物模型的可重复性、相似性和技术限制是有限的。
方法
我们使用粉色斑马-Danio-rerio 开发了一个中风诱导模型。通过给予斑马鱼D-葡萄糖 (111 mM) 14 天诱导斑马鱼糖尿病，研究中包括血糖水平高于 100 mg/dl 的斑马鱼。在斑马鱼中，单次口服内皮素-1 (ET-1, 3µl/gm) 可诱发实验性中风。游泳、行为模式和认知表现都使用 UMA Tracker 进行记录和分析。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 给药导致游泳模式和运动的统计学显着变化。此外，糖尿病 ET-1 治疗组游泳模式和恢复时间的变化具有统计学意义。在神经认知评估范式中，ET-1 治疗组的行为研究显示认知特征和运动协调受到干扰，错误数量增加，总行驶距离减少。与视顶盖和端脑的正常对照组相比，ET-1 治疗组的组织病理学分析显示，与正常对照组相比，ET-1 治疗组的皮质病变、萎缩的神经元细胞和球体形式的血小板与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，当前的实验模型优于其他可用的啮齿动物中风模型。结论：ET-1 诱导的实验性斑马鱼中风模型因其新颖性、可重复性和克服其他近期模型中发现的技术错误的能力，为糖尿病相关中风研究开辟了新途径。
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