endothelin-1 and Ischemic-Stroke

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.. 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.. 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.. 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.

Topics: Animals; Behavior, Animal; Blood Glucose; Blood Platelets; Brain Ischemia; Cognition; Diabetes Mellitus, Experimental; Disease Models, Animal; Endothelin-1; Female; Glucose; Ischemic Stroke; Male; Neurons; Psychomotor Performance; Swimming; Zebrafish

Acute ischemic stroke patients benefit from reperfusion in a short time-window after debut. Later treatment may be indicated if viable brain tissue is demonstrated and this outweighs the inherent risks of late reperfusion. Magnetic resonance imaging (MRI) with hyperpolarized [1-

Topics: Animals; Brain; Brain Infarction; Case-Control Studies; Cerebrovascular Circulation; Endothelin-1; Female; Humans; Ischemic Stroke; Magnetic Resonance Imaging; Models, Animal; Perfusion Imaging; Pyruvic Acid; Reperfusion; Swine

Topics: Animals; Blood Glucose; Cell Hypoxia; Cell Line; Cognitive Dysfunction; Culture Media; Diabetes Complications; Disease Models, Animal; Endothelin-1; Humans; Inflammation; Ischemic Stroke; Lipopolysaccharides; Mice; Microglia; Signal Transduction

The endothelin (ET) system has been implicated to contribute to the pathophysiology of cognitive impairment and stroke in experimental diabetes. Our goals were to test the hypotheses that (1) circulating and (or) periinfarct ET-1 levels are elevated after stroke in both sexes and this increase is greater in diabetes, (2) ET receptors are differentially regulated in the diabetic brain, (3) brain microvascular endothelial cells (BMVEC) of female and male origin express the ETA receptor subtype, and (4) diabetes- and stroke-mimicking conditions increase ET-1 levels in BMVECs of both sexes. Control and diabetic rats were randomized to sham or stroke surgery. BMVECs of male (hBEC5i) and female (hCMEC/D3) origin, cultured under normal and diabetes-mimicking conditions, were exposed to normoxia or hypoxia. Circulating ET-1 levels were higher in diabetic animals and this was more pronounced in the male cohort. Stroke did not further increase plasma ET-1. Tissue ET-1 levels were increased after stroke only in males, whereas periinfarct ET-1 increased in both control and diabetic females. Male BMVECs secreted more ET-1 than female cells and hypoxia increased ET-1 levels in both cell types. There was sexually dimorphic regulation of ET receptors in both tissue and cell culture samples. There are sex differences in the stroke- and diabetes-mediated changes in the brain ET system at the endothelial and tissue levels.

Topics: Animals; Brain; Cell Line; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Diet, High-Fat; Endothelial Cells; Endothelin-1; Endothelium, Vascular; Female; Humans; Ischemic Stroke; Male; Microvessels; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Sex Factors; Streptozocin