Executive Summary : | snakebite is a significant occupational hazard worldwide, with an annual mortality rate of 1300 to 50,000 in tropical countries like India. snake venom, primarily composed of PLA2, sVMP, sVsP, and other peptides, impairs the central nervous system, causing rapid immobilization or death of prey. The blood-brain barrier (BBB) is the mono-cellular interface that separates peripheral circulation from direct contact with the CNs. BBB is composed of endothelial cells with tight junctions (TJs), adherens junctions (AJs), gap junctions (GJs), basement membrane of extracellular matrix, astrocyte end-feet, and pericyte. Junctional membrane proteins regulate the BBB's permeability, while TJ scaffolding proteins, junctional adhesion molecules, and other junctional proteins are involved in its formation, organization, and maintenance. sVMPs, the major components of viper venoms, cleave the basement membrane and adhesion proteins of the endothelial cells-matrix complex, leading to the detachment of endothelial cells, thin capillary walls, and blood effusion. sVsPs of viper venoms have hemotoxic effects, such as blood coagulation, fibrinolysis, platelet aggregation, and blood pressure, potentially fatal for snakebite victims. Most snake venom cannot penetrate through BBB-TJs, but few researchers have reported that snake venom components could cross the BBB and enter the CNs. The proposed project aims to investigate viper venom-induced alterations in BBB homeostasis, emphasizing junctional protein complexes, to uncover new therapeutic strategies for envenomed patients. |