Abstract
Arginine-vasopressin (AVP) V-1 receptors are known to mediate brain edema formation after traumatic brain injury (TBI). So far, however, AVP V-1 receptors were only inhibited by genetic deletion or prior to trauma. Therefore, the current study aimed to determine the therapeutic window of AVP V-1 receptor 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 V-1 receptor 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 V-1 receptors within 1 h after TBI significantly reduced BWC from 81.6 +/- 0.7 to 80.6 +/- 0.7% (means +/- 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 +/- 2.5mm(3) vs. 30.1 +/- 2.0mm(3) in 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 V-1 receptors improve outcome after experimental TBI when given within a clinically relevant time window. Therefore, AVP V-1 receptors may represent a therapeutic target with clinical potential.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 0897-7151 |
| Sprache: | Englisch |
| Dokumenten ID: | 51015 |
| Datum der Veröffentlichung auf Open Access LMU: | 14. Jun. 2018, 09:45 |
| Letzte Änderungen: | 04. Nov. 2020, 13:28 |
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