Endothelial dysfunction abrogates the efficacy of normobaric hyperoxia in stroke

Area of Science:

• Neuroscience
• Cardiovascular Science
• Biomedical Engineering

Background:

• Normobaric hyperoxia shows promise for focal cerebral ischemia in experiments.
• Clinical trials yield inconsistent results, hindering patient care translation.
• Endothelial dysfunction, common in stroke patients, is understudied in hyperoxia research.

Purpose of the Study:

• Investigate how endothelial dysfunction affects normobaric hyperoxia's neuroprotective efficacy.
• Determine if endothelial nitric oxide synthase (eNOS) function is critical for hyperoxia's benefits.

Main Methods:

• Utilized hyperlipidemic apolipoprotein E knock-out and eNOS knock-out mice to model endothelial dysfunction.
• Employed high-resolution laser speckle and multispectral reflectance imaging to assess brain perfusion and oxygenation.
• Evaluated effects of normobaric hyperoxia during distal middle cerebral artery occlusion.

Main Results:

• In wild-type mice, hyperoxia improved perfusion, oxygenation, suppressed peri-infarct depolarizations, reduced infarct size, and enhanced neurological function.
• In mice with endothelial dysfunction, hyperoxia worsened perfusion and did not improve infarct volume or neurological outcomes.
• Beneficial effects of hyperoxia were critically dependent on eNOS function.

Conclusions:

• Endothelial dysfunction abrogates the neuroprotective effects of normobaric hyperoxia in ischemic stroke models.
• Vascular risk factors linked to endothelial dysfunction may identify non-responders to hyperoxia therapy.
• Findings have potential implications for hyperoxia's use in myocardial and systemic circulation.