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

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.

• Authors: Nikan H Khatibi, Lillian K Lee, Yilin Zhou, Wanqiu Chen, William Rolland, Nancy Fathali, Robert Martin, Richard Applegate, Gary Stier, John H Zhang
• Journal: Acta neurochirurgica. Supplement (Acta Neurochir Suppl) Vol. 111 Pg. 207-12 ( 2011) ISSN: 0065-1419 [Print] Austria
• PMID: 21725757 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Endothelin A Receptor Antagonists
• Pyrrolidines
• Receptor, Endothelin A
• Tetrazolium Salts
• triphenyltetrazolium
• Atrasentan

Topics

• Animals
• Animals, Newborn
• Atrasentan
• Brain Edema (etiology, prevention & control)
• Brain Infarction (etiology, prevention & control)
• Brain Injuries (drug therapy, etiology, metabolism)
• Endothelin A Receptor Antagonists
• Functional Laterality
• Hand Strength (physiology)
• Hypoxia-Ischemia, Brain (complications)
• Maze Learning (drug effects)
• Motor Activity (drug effects)
• Psychomotor Performance (drug effects)
• Pyrrolidines (therapeutic use)
• Rats
• Rats, Sprague-Dawley
• Receptor, Endothelin A (metabolism)
• Tetrazolium Salts