Arginine-vasopressin V 1a receptor inhibition improves neurologic outcomes following an intracerebral hemorrhagic brain injury

Abstract

Cerebral edema is a devastating consequence of brain injury leading to cerebral blood flow compromise and worsening parenchyma damage. In the present study, we investigated the effects of arginine-vasopressin (AVP) V 1a receptor inhibition following an intracerebral hemorrhagic (ICH) brain injury in mice and closely assessed the role it played in cerebral edema formation, neurobehavioral functioning, and blood–brain-barrier (BBB) disruption. To support our investigation, SR49059, an AVP V 1a receptor competitive antagonist, and NC1900, an arginine-vasopressin analogue, were used. Male CD1 mice ( n = 205) were randomly assigned to the following groups: naïve, sham, ICH, ICH with SR49059 at 0.5 mg/kg, ICH with SR49059 at 2 mg/kg, ICH with NC1900 at 1 ng/kg, ICH with NC1900 at 10 ng/kg, and ICH with a combination of SR49059 at 2 mg/kg and NC1900 at 10 ng/kg. ICH was induced by using the collagenase injection model and treatment was given 1 h after surgery. Post assessment was conducted at 6, 12, 24, and 72 h after surgery and included brain water content, neurobehavioral testing, Evans Blue assay, western blotting, and hemoglobin assay. The study found that inhibition of the AVP V 1a receptor significantly reduced cerebral edema at 24 and 72 h post-ICH injury and improved neurobehavioral function while reducing BBB disruption at 72 h. Western blot analysis demonstrated increased protein expression of aquaporin 4 (AQP4) in vehicle, which was reduced with AVP V 1a receptor inhibition. Our study suggests that blockage of the AVP V 1a receptor, is a promising treatment target for improving ICH-induced brain injury. Further studies will be needed to confirm this relationship and determine future clinical direction.