Normobaric hyperoxia improves cerebral blood flow and oxygenation, and inhibits peri-infarct depolarizations in experimental focal ischaemia.

Abstract

Normobaric hyperoxia is under investigation as a treatment for acute ischaemic stroke. In experimental models, normobaric hyperoxia reduces cerebral ischaemic injury and improves functional outcome. The mechanisms of neuroprotection are still debated because, (i) inhalation of 100% O2 does not significantly increase total blood O2 content; (ii) it is not known whether normobaric hyperoxia increases O2 delivery to the severely ischaemic cortex because of its short diffusion distance; and (iii) hyperoxia may reduce collateral cerebral blood flow (CBF) to ischaemic penumbra because it can cause vasoconstriction. We addressed these issues using real-time two-dimensional multispectral reflectance imaging and laser speckle flowmetry to simultaneously and non-invasively determine the impact of normobaric hyperoxia on CBF and oxygenation in ischaemic cortex. Ischaemia was induced by distal middle cerebral artery occlusion (dMCAO) in normoxic (30% inhaled O2, arterial pO2 134 +/- 9 mmHg), or hyperoxic mice (100% inhaled O2 starting 15 min after dMCAO, arterial pO2 312 +/- 10 mmHg). Post-ischaemic normobaric hyperoxia caused an immediate and progressive increase in oxyhaemoglobin (oxyHb) concentration, nearly doubling it in ischaemic core within 60 min. In addition, hyperoxia improved CBF so that the area of cortex with < or =20% residual CBF was decreased by 45% 60 min after dMCAO. Furthermore, hyperoxia reduced the frequency of peri-infarct depolarizations (PIDs) by more than 60%, and diminished their deleterious effects on CBF and metabolic load. Consistent with these findings, infarct size was reduced by 45% in the hyperoxia group 2 days after 75 min transient dMCAO. Our data show that normobaric hyperoxia increases tissue O2 delivery, and that novel mechanisms such as CBF augmentation, and suppression of PIDs may afford neuroprotection during hyperoxia.

• Authors: Hwa Kyoung Shin, Andrew K Dunn, Phillip B Jones, David A Boas, Eng H Lo, Michael A Moskowitz, Cenk Ayata
• Journal: Brain : a journal of neurology (Brain) Vol. 130 Issue Pt 6 Pg. 1631-42 (Jun 2007) ISSN: 1460-2156 [Electronic] England
• PMID: 17468117 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins

Topics

• Animals
• Cerebrovascular Circulation
• Disease Models, Animal
• Hemoglobins (metabolism)
• Infarction, Middle Cerebral Artery (pathology, physiopathology, therapy)
• Mice
• Mice, Inbred C57BL
• Oxygen Consumption
• Oxygen Inhalation Therapy
• Treatment Outcome