title: Time-Dependent Effects of Arginine-Vasopressin V1 Receptor Inhibition on Secondary Brain Damage after Traumatic Brain Injury.
abstract: Arginine-vasopressin (AVP) V1receptors are known to mediate brain edema formation after traumatic brain injury (TBI). So far, however, AVP V1receptors were only inhibited by genetic deletion or prior to trauma. Therefore, the current study aimed to determine the therapeutic window of AVP V1receptor antagonization after TBI. Male C57BL/6 mice (n = 7 per group) were subjected to controlled cortical impact (CCI), and 500 ng of a selective peptide V1receptor antagonist (V1880) were applied by intracerebroventricular injection 5 min, and 1, 3, and 6 h thereafter. After 24 h, brain water content (BWC), intracranial pressure (ICP), and secondary contusion expansion volume were assessed. Neurological function was assessed daily for 7 days after trauma. Inhibition of AVP V1receptors within 1 h after TBI significantly reduced BWC from 81.6 ± 0.7 to 80.6 ± 0.7% (mean ± SD; p < 0.05). Reduction of brain edema resulted in a significant decrease in ICP from 25.9 ± 1.8 mm Hg to 21.0 ± 1.5 mm Hg (p < 0.05) and a reduction in contusion volume (26.1 ± 2.5 mm3vs. 30.1 ± 2.0 mm3in controls; p < 0.05). This reduction of brain injury resulted in a significantly improved neurological function 7 days after trauma. Treatments initiated 6 h after TBI had no effect. The results of the current study demonstrate that inhibition of AVP V1receptors improve outcome after experimental TBI when given within a clinically relevant time window. Therefore, AVP V1receptors may represent a therapeutic target with clinical potential.
authors.affiliation: 1 Laboratory of Experimental Neurosurgery , LMU Munich, Munich, Germany .
authors.forename: Sandro M
authors.initials: SM
authors.lastname: Krieg
authors.affiliation: 1 Laboratory of Experimental Neurosurgery , LMU Munich, Munich, Germany .|2 Department of Neurosurgery , LMU Munich, Munich, Germany .
authors.forename: Raimund
authors.initials: R
authors.lastname: Trabold
authors.affiliation: 1 Laboratory of Experimental Neurosurgery , LMU Munich, Munich, Germany .|3 Institute for Stroke and Dementia Research , LMU Munich, Munich, Germany .|4 Munich Cluster for Systems Neurology , LMU Munich, Munich, Germany .
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000494:pharmacology; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D000070642:Brain Injuries, Traumatic / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D007427:Intracranial Pressure / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017483:Receptors, Vasopressin / Q000187:drug effects*; D013997:Time Factors
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; C549395:vasopressin, deaminoPen(1)-O-Me-Tyr(2)-Arg(8)-; D001127:Arginine Vasopressin
keywords: AVP; ICP; TBI; brain edema; secondary brain damage