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

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.