title: 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: Department of Anesthesiology, Loma Linda Medical Center, Loma Linda, CA, USA.
authors: Nikan H
authors: NH
authors: Khatibi
authors: Lillian K
authors: LK
authors: Lee
authors: Yilin
authors: Y
authors: Zhou
authors: Wanqiu
authors: W
authors: Chen
authors: William
authors: W
authors: Rolland
authors: Nancy
authors: N
authors: Fathali
authors: Robert
authors: R
authors: Martin
authors: Richard
authors: R
authors: Applegate
authors: Gary
authors: G
authors: Stier
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000077868:Atrasentan; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D065130:Endothelin A Receptor Antagonists; D007839:Functional Laterality; D018737:Hand Strength / Q000502:physiology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications*; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism*; D013778:Tetrazolium Salts
chemical_list: D065130:Endothelin A Receptor Antagonists; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D000077868:Atrasentan