No 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.

Shale matrix pore structure controls the gas storage mechanism and gas transport behaviors. We employed various techniques to characterize the complex pore structures of 12 shale samples collected from two marine shale formations in upper Yangtze area in China. The characterization techniques include field emission scanning electron microscopy (FE-SEM), high-pressure mercury intrusion porosimetry (MIP), and low-pressure N 2 /CO 2 adsorption. The excess methane adsorption capacity was measured for each samples and results were modeled using Langmuir model. Based on the FE-SEM image analyses, micro-and meso-pores within organic matter and inter-particle pores between or within clay minerals are the most commonly developed in these shale samples. Both uni-and multi-modal pore size distributions (PSDs) were observed, and a significant portion of pores are in the pore size range between 3 and 100 nm. It was also found that the micropore (<2 nm) is the major contributor to the overall specific surface area (SSA), whereas most of the pore volume is occupied by mesopores (2-50 nm). Two different fractal

Summary:Stroke causes heterogeneous changes in tissue oxygenation, with a region of decreased blood flow, the penumbra, surrounding a severely damaged ischemic core. Treatment of acute ischemic stroke aims to save this penumbra before its irreversible damage by continued ischemia. However, effective treatment remains elusive due to incomplete understanding of processes leading to penumbral death. While oxygenation is central in ischemic neuronal death, it is unclear exactly what actual changes occur in interstitial oxygen tension (pO 2 ) in ischemic regions during stroke, particularly the penumbra. Using the unique capability of in vivo electron paramagnetic resonance (EPR) oximetry to measure localized interstitial pO 2 , we measured both absolute values, and temporal changes of pO 2 in ischemic penumbra and core during ischemia and reperfusion in a rat model. Ischemia rapidly decreased interstitial pO 2 to 32% ± 7.6% and 4% ± 0.6% of pre-ischemic values in penumbra and core, respectively 1 hour after ischemia. Importantly, whilst reperfusion restored core pO 2 close to its pre-ischemic value, penumbral pO 2 only partially recovered. Hyperoxic treatment significantly increased penumbral pO 2 during ischemia, but not in the core, and also increased penumbral pO 2 during reperfusion. These divergent, important changes in pO 2 in penumbra and core were explained by combined differences in cellular oxygen consumption rates and microcirculation conditions. We therefore demonstrate that interstitial pO 2 in penumbra and core is differentially affected during ischemia and reperfusion, providing new insights to the pathophysiology of stroke. The results support normobaric hyperoxia as a potential early intervention to save penumbral tissue in acute ischemic stroke.

Translational stroke research is a challenging task that needs long term team work of the stroke research community. Highly reproducible stroke models with excellent outcome consistence are essential for obtaining useful data from preclinical stroke trials as well as for improving inter-lab comparability. However, our review of literature shows that the infarct variation coefficient of commonly performed stroke models ranges from 5% to 200%. An overall improvement of the commonly used stroke models will further improve the quality for experimental stroke research as well as inter-lab comparability. Many factors play a significant role in causing outcome variation; however, they have not yet been adequately addressed in the Stroke Therapy Academic Industry Roundtable (STAIR) recommendations and the Good Laboratory Practice (GLP). These critical factors include selection of anesthetics, maintenance of animal physiological environment, stroke outcome observation, and model specific factors that affect success rate and variation. The authors have reviewed these major factors that have been reported to influence stroke model outcome, herewith, provide the first edition of stroke model guidelines so to initiate active discussion on this topic. We hope to reach a general agreement among stroke researchers in the near future with its successive updated versions.