Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic brain injury in rats

Nikan H. Khatibi, Lillian K. Lee, Yilin Zhou, Wanqiu Chen, William Rolland, Nancy Fathali, Robert Martin, Richard Lee Applegate, Gary Stier, John H. Zhang

Research output: Chapter in Book/Report/Conference proceedingConference contribution

3 Scopus citations

Abstract

Cerebral hypoxia-ischemia (HI) is an important cause of mortality and disability in newborns. It is a result of insufficient oxygen and glucose circulation to the brain, initiating long-term cerebral damage and cell death. Emerging evidence suggests that endothelin receptor-A (ETA) activation can play an important role in mediating brain damage. In this study, we investigated the role of ETA receptor inhibition using ABT-627 in neonatal HI injured rats. Postnatal day 10 Sprague-Dawley rat pups (n = 91) were assigned to the following groups: sham (n = 28), HI (vehicle, n = 32), and HI with ABT-627 at 3 mg/kg (n = 31). The Rice-Vannucci model was used to induce ischemia by ligating the right common carotid artery, followed by a 2 h hypoxic episode using 8% oxygen in a 37°C chamber. Postoperative assessment was conducted at 48 h after injury and again at 4 weeks. At the acute time point, investigative markers included cerebral edema, infarction volume, and body weight change. Neurobehavioral testing was measured at 4 weeks post-injury. Our findings indicated that ABT-627 had no effect on the measured parameters. This study suggests that ETA receptor blockade using ABT-627 post-treatment fails to improve neurological outcomes in neonatal HI injured rats.

Original languageEnglish (US)
Title of host publicationIntracerebral Hemorrhage Research: From Bench to Bedside
PublisherSpringer-Verlag Wien
Pages207-212
Number of pages6
Edition111
ISBN (Print)9783709106921
DOIs
StatePublished - 2011
Externally publishedYes

Publication series

NameActa Neurochirurgica, Supplementum
Number111
ISSN (Print)00651419
ISSN (Electronic)00016268

Keywords

  • ABT-627
  • Brain injury
  • Endothelins
  • Hypoxic-ischemic (HI)

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Khatibi, N. H., Lee, L. K., Zhou, Y., Chen, W., Rolland, W., Fathali, N., Martin, R., Applegate, R. L., Stier, G., & Zhang, J. H. (2011). Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic brain injury in rats. In Intracerebral Hemorrhage Research: From Bench to Bedside (111 ed., pp. 207-212). (Acta Neurochirurgica, Supplementum; No. 111). Springer-Verlag Wien. https://doi.org/10.1007/978-3-7091-0693-8_35