Arginine-vasopressin V1a receptor inhibition improves neurologic outcomes following an intracerebral hemorrhagic brain injury

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) V1a 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 V1a 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 V1a 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 V1a receptor inhibition. Our study suggests that blockage of the AVP V1a 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.

Research highlights▶ AVP V1a receptor inhibitor SR49059 decreases the ICH-induced brain edema. ▶ SR49059 ameliorates neurological deficits in ICH model of brain injury. ▶ SR49059 effect modulates AQP4 activity in the brain after ICH. ▶ AVP V1a receptor activator has no distinct effect but reverses the V1a receptor inhibitor effect.