Blockade of Arginine Vasopressin receptors prevents blood-brain barrier breakdown in Experimental Autoimmune Encephalomyelitis.

ABSTRACT: The blood-brain barrier (BBB) plays a significant pathophysiological role in multiple sclerosis (MS). Vasopressin (AVP) is released after brain injury and contributes to the inflammatory response. We propose that AVP may be modulating BBB permeability and hence affecting EAE clinical signs. Female Lewis rats were immunized s.c. with guinea-pig brain extract suspended in complete Freund's adjuvant. Prior to that, animals were subjected to Neurointermediate pituitary lobectomy (NIL) or treated with AVP receptor antagonist (conivaptan). BBB permeability assays were performed. Western blot for claudin-5 and histological analysis were performed in conivaptan treated EAE rats. EAE increase in BBB permeability to Evans blue was reverted by the NIL surgery. AVP receptor blockade reverted the EAE BBB hyperpermeability to Evans blue and 10-kDa FITC-dextran in almost all brain regions. Both, AVP low levels and AVP receptor blockade attenuated EAE clinical signs. Conivaptan reduced perivascular cuffs in EAE rats. A decrease in claudin-5 expression was observed in EAE rats and conivaptan treatment partially restored normal levels. Our data indicate that V1a and V2 AVP receptors can modulate BBB permeability and consequently are involved in the CNS inflammatory process during EAE. Future research is required to characterize the utility of vasopressin antagonist in MS treatment.

SUBMITTER: Vinuela-Berni V 

PROVIDER: S-EPMC6965180 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature