Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke

Hwa Kyoung Shin, Fumiaki Oka, Ji Hyun Kim, Dmitriy Atochin, Paul L. Huang, Cenk Ayata

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hyperoxia has been uniformly efficacious in experimental focal cerebral ischemia. However, pilot clinical trials have showed mixed results slowing its translation in patient care. To explain the discordance between experimental and clinical outcomes, we tested the impact of endothelial dysfunction, exceedingly common in stroke patients but under-represented in experimental studies, on the neuroprotective efficacy of normobaric hyperoxia.Weused hyperlipidemic apolipoproteinEknock-out and endothelial nitric oxide synthase knock-out mice as models of endothelial dysfunction, and examined the effects of normobaric hyperoxia on tissue perfusion and oxygenation using high-resolution combined laser speckle and multispectral reflectance imaging during distal middle cerebral artery occlusion. In normal wild-type mice, normobaric hyperoxia rapidly and significantly improved tissue perfusion and oxygenation, suppressed peri-infarct depolarizations, reduced infarct volumes, and improved neurological function. In contrast, normobaric hyperoxia worsened perfusion in ischemic brain and failed to reduce infarct volumes or improve neurological function in mice with endothelial dysfunction. These data suggest that the beneficial effects of hyperoxia on ischemic tissue oxygenation, perfusion, and outcome are critically dependent on endothelial nitric oxide synthase function. Therefore, vascular risk factors associated with endothelial dysfunction may predict normobaric hyperoxia nonresponders in ischemic stroke. These data may have implications for myocardial and systemic circulation as well.

Original languageEnglish
Pages (from-to)15200-15207
Number of pages8
JournalJournal of Neuroscience
Volume34
Issue number46
DOIs
Publication statusPublished - 12 Nov 2014
Externally publishedYes

Fingerprint

Hyperoxia
Stroke
Perfusion
Nitric Oxide Synthase Type III
Middle Cerebral Artery Infarction
Brain Ischemia
Knockout Mice
Patient Care
Lasers
Clinical Trials
Brain

Keywords

  • Cerebral blood flow
  • Focal cerebral ischemia
  • Laser speckle imaging
  • Multispectral reflectance imaging
  • Optical imaging
  • Viability threshold

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke. / Shin, Hwa Kyoung; Oka, Fumiaki; Kim, Ji Hyun; Atochin, Dmitriy; Huang, Paul L.; Ayata, Cenk.

In: Journal of Neuroscience, Vol. 34, No. 46, 12.11.2014, p. 15200-15207.

Research output: Contribution to journalArticle

Shin, Hwa Kyoung ; Oka, Fumiaki ; Kim, Ji Hyun ; Atochin, Dmitriy ; Huang, Paul L. ; Ayata, Cenk. / Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke. In: Journal of Neuroscience. 2014 ; Vol. 34, No. 46. pp. 15200-15207.
@article{4b71930c469f4f7483e52fa37bc4b5b4,
title = "Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke",
abstract = "Hyperoxia has been uniformly efficacious in experimental focal cerebral ischemia. However, pilot clinical trials have showed mixed results slowing its translation in patient care. To explain the discordance between experimental and clinical outcomes, we tested the impact of endothelial dysfunction, exceedingly common in stroke patients but under-represented in experimental studies, on the neuroprotective efficacy of normobaric hyperoxia.Weused hyperlipidemic apolipoproteinEknock-out and endothelial nitric oxide synthase knock-out mice as models of endothelial dysfunction, and examined the effects of normobaric hyperoxia on tissue perfusion and oxygenation using high-resolution combined laser speckle and multispectral reflectance imaging during distal middle cerebral artery occlusion. In normal wild-type mice, normobaric hyperoxia rapidly and significantly improved tissue perfusion and oxygenation, suppressed peri-infarct depolarizations, reduced infarct volumes, and improved neurological function. In contrast, normobaric hyperoxia worsened perfusion in ischemic brain and failed to reduce infarct volumes or improve neurological function in mice with endothelial dysfunction. These data suggest that the beneficial effects of hyperoxia on ischemic tissue oxygenation, perfusion, and outcome are critically dependent on endothelial nitric oxide synthase function. Therefore, vascular risk factors associated with endothelial dysfunction may predict normobaric hyperoxia nonresponders in ischemic stroke. These data may have implications for myocardial and systemic circulation as well.",
keywords = "Cerebral blood flow, Focal cerebral ischemia, Laser speckle imaging, Multispectral reflectance imaging, Optical imaging, Viability threshold",
author = "Shin, {Hwa Kyoung} and Fumiaki Oka and Kim, {Ji Hyun} and Dmitriy Atochin and Huang, {Paul L.} and Cenk Ayata",
year = "2014",
month = "11",
day = "12",
doi = "10.1523/JNEUROSCI.1110-14.2014",
language = "English",
volume = "34",
pages = "15200--15207",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "46",

}

TY - JOUR

T1 - Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke

AU - Shin, Hwa Kyoung

AU - Oka, Fumiaki

AU - Kim, Ji Hyun

AU - Atochin, Dmitriy

AU - Huang, Paul L.

AU - Ayata, Cenk

PY - 2014/11/12

Y1 - 2014/11/12

N2 - Hyperoxia has been uniformly efficacious in experimental focal cerebral ischemia. However, pilot clinical trials have showed mixed results slowing its translation in patient care. To explain the discordance between experimental and clinical outcomes, we tested the impact of endothelial dysfunction, exceedingly common in stroke patients but under-represented in experimental studies, on the neuroprotective efficacy of normobaric hyperoxia.Weused hyperlipidemic apolipoproteinEknock-out and endothelial nitric oxide synthase knock-out mice as models of endothelial dysfunction, and examined the effects of normobaric hyperoxia on tissue perfusion and oxygenation using high-resolution combined laser speckle and multispectral reflectance imaging during distal middle cerebral artery occlusion. In normal wild-type mice, normobaric hyperoxia rapidly and significantly improved tissue perfusion and oxygenation, suppressed peri-infarct depolarizations, reduced infarct volumes, and improved neurological function. In contrast, normobaric hyperoxia worsened perfusion in ischemic brain and failed to reduce infarct volumes or improve neurological function in mice with endothelial dysfunction. These data suggest that the beneficial effects of hyperoxia on ischemic tissue oxygenation, perfusion, and outcome are critically dependent on endothelial nitric oxide synthase function. Therefore, vascular risk factors associated with endothelial dysfunction may predict normobaric hyperoxia nonresponders in ischemic stroke. These data may have implications for myocardial and systemic circulation as well.

AB - Hyperoxia has been uniformly efficacious in experimental focal cerebral ischemia. However, pilot clinical trials have showed mixed results slowing its translation in patient care. To explain the discordance between experimental and clinical outcomes, we tested the impact of endothelial dysfunction, exceedingly common in stroke patients but under-represented in experimental studies, on the neuroprotective efficacy of normobaric hyperoxia.Weused hyperlipidemic apolipoproteinEknock-out and endothelial nitric oxide synthase knock-out mice as models of endothelial dysfunction, and examined the effects of normobaric hyperoxia on tissue perfusion and oxygenation using high-resolution combined laser speckle and multispectral reflectance imaging during distal middle cerebral artery occlusion. In normal wild-type mice, normobaric hyperoxia rapidly and significantly improved tissue perfusion and oxygenation, suppressed peri-infarct depolarizations, reduced infarct volumes, and improved neurological function. In contrast, normobaric hyperoxia worsened perfusion in ischemic brain and failed to reduce infarct volumes or improve neurological function in mice with endothelial dysfunction. These data suggest that the beneficial effects of hyperoxia on ischemic tissue oxygenation, perfusion, and outcome are critically dependent on endothelial nitric oxide synthase function. Therefore, vascular risk factors associated with endothelial dysfunction may predict normobaric hyperoxia nonresponders in ischemic stroke. These data may have implications for myocardial and systemic circulation as well.

KW - Cerebral blood flow

KW - Focal cerebral ischemia

KW - Laser speckle imaging

KW - Multispectral reflectance imaging

KW - Optical imaging

KW - Viability threshold

UR - http://www.scopus.com/inward/record.url?scp=84909953322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84909953322&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.1110-14.2014

DO - 10.1523/JNEUROSCI.1110-14.2014

M3 - Article

VL - 34

SP - 15200

EP - 15207

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 46

ER -