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

Vishal Chavda; Snehal Patel; Badrah S Alghamdi; Ghulam Md Ashraf

doi:10.1016/j.jchemneu.2021.102025

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

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

Authors

Vishal Chavda¹, Snehal Patel², Badrah S Alghamdi³, Ghulam Md Ashraf⁴

Affiliations

¹ Department of Pharmacology, Nirma University, Ahmadabad, Gujarat, India.
² Department of Pharmacology, Nirma University, Ahmadabad, Gujarat, India. Electronic address: snehal.pharma53@gmail.com.
³ Department of Physiology, Neuroscience Unit, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; Pre-Clinical Research Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Pre-Clinical Research Unit, King Fahd Medical Research Centre, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.

PMID: 34520802
DOI: 10.1016/j.jchemneu.2021.102025

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.

Keywords: Brain injury; Cerebrovascular stroke; Diabetes; Preproendothelin-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Behavior, Animal / drug effects
Blood Glucose / analysis
Blood Glucose / metabolism
Blood Platelets / pathology
Brain Ischemia / chemically induced*
Brain Ischemia / pathology
Cognition / drug effects
Diabetes Mellitus, Experimental / complications
Disease Models, Animal
Endothelin-1 / toxicity*
Female
Glucose
Ischemic Stroke / chemically induced*
Ischemic Stroke / pathology
Male
Neurons / pathology
Psychomotor Performance / drug effects
Swimming
Zebrafish

Substances

Blood Glucose
Endothelin-1
Glucose