P-BN006. Post exposure of anti-diabetic agents exerts neuroprotection and improve memory and learning in endothelin-1 induced global ischemia in adult zebrafish

Abstract

Introduction . Stroke is the recurrent threat of mortality worldwide among normal population and 3 fold more in diabetics. Current study was designed to elucidate the neuroprotective role of anti-diabetic agents in endothelin-1 induced global ischemia in adult zebrafish. Method . In our study, pink zebra-Daniorerio was used for induction of stroke. Diabetes was induced with 111 mM D-glucose for 14 days and zebrafish having more than 100 mg/dl blood glucose level were included in study. The experimental stroke was induced with single oral administration of Endothelin-1 3 µl/gm of zebrafish. Post treatment with anti-diabetic agents was carried out for 7 days after stroke. The swimming, behavioural-patterns and cognitive performance (Y-maze, T-maze) was recorded and analysed with UMA Tracker. The brains were extracted for histopathological investigations. Results . Administration of ET-1 in normal and diabetic group showed statistically significant (p<0.001) change in behavioural swimming patterns and movements (circulatory, irregular, disturbed, rotating) and delayed recovery time from stroke to normal swimming. Behavioural study of ET-1 treated groups showed disturbed cognitive profile and locomotors coordination (p<0.001) by increasing in the number of mistakes and reducing total distance travelled in neurocognitive assessment paradigm. Histopathological analysis of ET-1 treated groups indicated cortical lesions, shrinked neuronal cells and activated thrombocytes with disturbed normal flora of brain compared to normal control. Anti-diabetic treatment with voglibose and sexagliptin showed significant improvement upon post treatment in all neurological and behavioural assessment (p<0.005). Conclusion . Upon the data of this investigation, we concluded that among all the anti-diabetic agents (voglibose, saxagliptin, repaglinide and dapaglifozin) voglibose and sexagliptin showed significant improvement in neurological fitness and improved learning and cognitive profile in post stroke adult zebrafish. Keywords: Adult zebrafish, cerebrovascular stroke, neuroprotection, cognitive decline.