Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260

Research output: Chapter in Book/Report/Conference proceedingChapter

10 Citations (Scopus)

Abstract

The numerous situations which can result in cerebral hypoxic damage occur in newborn infants and in the elderly. In research aimed at more effective therapeutic intervention in ischaemic disorders of the brain, the animal model used and the principles of the causal therapy should be better outlined. The effects of the non-peptide AVPR (V2) antagonist 5-dimethylamino-1-[4-(2-methylbenzoylamino) benzoyl]-2,3,4,5-tetrahydro-1H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by general cerebral hypoxia were studied in rats. The general cerebral hypoxia was produced by bilateral common carotid ligation in Sprague-Dawley rats of the CFY strain. By 6 h after the ligation, half of the rats had died, but the survival rate was significantly higher following OPC-31260 administration. Electron microscopic examinations revealed typical ischaemic changes after the carotid ligation, and OPC-31260 treatment did not significantly reduce the hypoxic signs in the brain cortex; only a certain decrease in the pericapillary oedema was observed. The carotid ligation increased the brain contents of water and Na+ and enhanced the plasma AVP level. The increased brain water and Na+ accumulation was prevented by OPC-31260 administration, but the plasma AVP level was further enhanced by OPC-31260. These results demonstrate the important role of AVP in the development of the disturbances in brain water and electrolyte balance in response to general cerebral hypoxia. The carotid ligation-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on the renal AVPR (V2). These observations might suggest an effective approach to the treatment of global hypoxia-induced cerebral oedema in humans.

Original languageEnglish
Title of host publicationAdvances in Vasopressin and Oxytocin - From Genes to Behaviour to Disease
EditorsInga Neumann, Rainer Landgraf
Pages519-525
Number of pages7
DOIs
Publication statusPublished - Jul 28 2008

Publication series

NameProgress in Brain Research
Volume170
ISSN (Print)0079-6123

Keywords

  • carotid ligation
  • cerebral oedema
  • hyponatraemia
  • non-peptide
  • vasopressin receptor antagonist

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260'. Together they form a unique fingerprint.

  • Cite this

    Molnár, A. H., Varga, C., Berkó, A., Rojik, I., Párducz, Á., László, F., & László, F. A. (2008). Prevention of hypoxic brain oedema by the administration of vasopressin receptor antagonist OPC-31260. In I. Neumann, & R. Landgraf (Eds.), Advances in Vasopressin and Oxytocin - From Genes to Behaviour to Disease (pp. 519-525). (Progress in Brain Research; Vol. 170). https://doi.org/10.1016/S0079-6123(08)00439-1