TY - GEN
T1 - Endothelin receptor-A (ETa) inhibition fails to improve neonatal hypoxic-ischemic brain injury in rats
AU - Khatibi, Nikan H.
AU - Lee, Lillian K.
AU - Zhou, Yilin
AU - Chen, Wanqiu
AU - Rolland, William
AU - Fathali, Nancy
AU - Martin, Robert
AU - Applegate, Richard Lee
AU - Stier, Gary
AU - Zhang, John H.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - ABT-627
KW - Brain injury
KW - Endothelins
KW - Hypoxic-ischemic (HI)
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U2 - 10.1007/978-3-7091-0693-8_35
DO - 10.1007/978-3-7091-0693-8_35
M3 - Conference contribution
C2 - 21725757
AN - SCOPUS:79960673099
SN - 9783709106921
T3 - Acta Neurochirurgica, Supplementum
SP - 207
EP - 212
BT - Intracerebral Hemorrhage Research: From Bench to Bedside
PB - Springer-Verlag Wien
ER -