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) 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 2mg/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 1h 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.
Department of Physiology and Pharmacology, Loma Linda University, United States.
Anatol
A
Manaenko
Nancy
N
Fathali
Nikan H
NH
Khatibi
Tim
T
Lekic
Yu
Y
Hasegawa
Robert
R
Martin
Jiping
J
Tang
John H
JH
Zhang
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001522:Behavior, Animal; D001784:Blood Gas Analysis; D001794:Blood Pressure; D001929:Brain Edema / Q000503:physiopathology; D020202:Cerebral Hemorrhage, Traumatic / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009483:Neuropsychological Tests; D009842:Oligopeptides / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D065092:Antidiuretic Hormone Receptor Antagonists; D007211:Indoles; C115056:NC 1900; D009842:Oligopeptides; D011759:Pyrrolidines; C082134:relcovaptan; D011761:Pyrrolidonecarboxylic Acid
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