eNOS uncoupling in the cerebellum after BBB disruption by exposure to Phoneutria nigriventer spider venom.

摘要: Abstract Numerous studies have shown that the venom of Phoneutria nigriventer (PNV) armed-spider causes excitotoxic signals and blood–brain barrier breakdown (BBBb) in rats. Nitric oxide (NO) is a signaling molecule which has role endothelium homeostasis vascular health. The present study investigated relevance endothelial NO synthase (eNOS) uncoupling to clinical neurotoxic evolution induced by PNV. eNOS immunoblotting cerebellum lysates processed through low-temperature SDS-PAGE revealed significant increased monomerization enzyme at critical periods severe envenoming (1–2 h), whereas dimerization reversal paralleled amelioration animals condition (5–72 h). Moreover, was accompanied expression calcium-sensing calmodulin protein calcium-binding calbindin-D28 cerebellar neurons. It known greater monomers than dimers implies inability produce leading superoxide production endothelial/vascular dysfunction. We suggest transient deactivation disturbances calcium handling reduce enhance free radicals thus contributing dysfunction envenomed In addition, compromises capacity respond shear stress perivascular edema it one mechanisms involved BBBb promoted