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 Applegate; Gary Stier; John H. Zhang

doi:10.1007/978-3-7091-0693-8_35

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 Applegate, Gary Stier, John H. Zhang

Research output: Chapter in Book/Report/Conference proceeding › Chapter

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 (ET_A) activation can play an important role in mediating brain damage. In this study, we investigated the role of ET_A 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 ET_A receptor blockade using ABT-627 post-treatment fails to improve neurological outcomes in neonatal HI injured rats.

Original language	American English
Title of host publication	Intracerebral Hemorrhage Research
Subtitle of host publication	From Bench to Bedside
Publisher	Springer-Verlag Wien
Pages	207-212
Number of pages	6
Volume	111
Edition	111
ISBN (Print)	9783709106921
DOIs	https://doi.org/10.1007/978-3-7091-0693-8_35
State	Published - Jan 1 2011

Publication series

Name	Acta Neurochirurgica, Supplementum
Number	111
ISSN (Print)	0065-1419
ISSN (Electronic)	0001-6268

ASJC Scopus Subject Areas

Surgery
Clinical Neurology

Keywords

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

Disciplines

Anesthesiology
Medicine and Health Sciences
Endocrinology, Diabetes, and Metabolism

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Khatibi, N. H., Lee, L. K., Zhou, Y., Chen, W., Rolland, W., Fathali, N., Martin, R., Applegate, R., 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., Vol. 111, pp. 207-212). (Acta Neurochirurgica, Supplementum; No. 111). Springer-Verlag Wien. https://doi.org/10.1007/978-3-7091-0693-8_35

Endothelin Receptor-A (ETa) Inhibition Fails to Improve Neonatal Hypoxic-Ischemic Brain Injury in Rats. / Khatibi, Nikan H.; Lee, Lillian K.; Zhou, Yilin et al.
Intracerebral Hemorrhage Research: From Bench to Bedside. Vol. 111 111. ed. Springer-Verlag Wien, 2011. p. 207-212 (Acta Neurochirurgica, Supplementum; No. 111).

Research output: Chapter in Book/Report/Conference proceeding › Chapter

Khatibi, NH, Lee, LK, Zhou, Y, Chen, W, Rolland, W, Fathali, N, Martin, R, Applegate, R, Stier, G & Zhang, JH 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 edn, vol. 111, Acta Neurochirurgica, Supplementum, no. 111, Springer-Verlag Wien, pp. 207-212. https://doi.org/10.1007/978-3-7091-0693-8_35

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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.",

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AU - Fathali, Nancy

AU - Martin, Robert

AU - Applegate, Richard

AU - Stier, Gary

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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.

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ER -

Endothelin Receptor-A (ETa) Inhibition Fails to Improve Neonatal Hypoxic-Ischemic Brain Injury in Rats

Abstract

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ASJC Scopus Subject Areas

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