title: Electron paramagnetic resonance-guided normobaric hyperoxia treatment protects the brain by maintaining penumbral oxygenation in a rat model of transient focal cerebral ischemia.
abstract: Oxygen therapy for ischemic stroke remains controversial. Too much oxygen may lead to oxidative stress and free radical damage while too little oxygen will have minimal therapeutic effect. In vivo electron paramagnetic resonance (EPR) oximetry, which can measure localized interstitial partial oxygen (pO2), can monitor penumbral changes of pO2. Therefore, we used EPR to study the effects of oxygen therapy in a rat model of 90-mins middle cerebral artery occlusion (MCAO). We found that 95% normobaric O2 given during ischemia was able to maintain penumbral interstitial pO2 levels close to the preischemic value while it may cause a two-fold increase in penumbral pO2 level if given during reperfusion. Elevation of the penumbra pO2 to preischemic physiologic level during MCAO significantly reduced infarction volume, improved neurologic function, decreased the generation of reactive oxygen species (ROS), and reduced matrix metalloproteinase (MMP)-9 expression and caspase-8 cleavage in the penumbra tissue of rats brain treated with oxygen. These results suggest that maintaining penumbral oxygenation by normobaric oxygen treatment during ischemia lead to neuroprotection, which is further reflected by the decreased production of ROS, MMP-9, and caspase-8.
authors.affiliation: College of Pharmacy, Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico 87131-0001, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Liu
authors.forename: Wenlan
authors.initials: W
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Ding
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyake
authors.forename: Gary A
authors.initials: GA
authors.lastname: Rosenberg
authors.forename: Ke Jian
authors.initials: KJ
authors.lastname: Liu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001794:Blood Pressure; D020169:Caspases / Q000378:metabolism; D002560:Cerebrovascular Circulation; D002851:Chromatography, High Pressure Liquid; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D018496:Hyperoxia / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control* / Q000628:therapy; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage* / Q000378:metabolism* / Q000627:therapeutic use; D010102:Oxygen Inhalation Therapy / Q000379:methods*; D010313:Partial Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D000080242:8-Hydroxy-2'-Deoxyguanosine; D020169:Caspases; D020782:Matrix Metalloproteinases; D003849:Deoxyguanosine; D010100:Oxygen