Effects of stroke severity and treatment duration in normobaric hyperoxia treatment of ischemic stroke

In order to improve clinical trial design and translation of normobaric oxygen (NBO) treatment of ischemic stroke, NBO treatment parameters need to be better understood. This study investigated NBO treatment efficacy at two different stroke severities and two NBO treatment durations in rats. For the 60-min middle cerebral artery occlusion (MCAO), NBO treatment for 25 min and 150 min were studied. For the 90-min MCAO, NBO treatment for 55 min and 150 min were studied. Cerebral blood flow (CBF), apparent diffusion coefficients (ADC) and T2 MRI were acquired during occlusion prior to treatment, after reperfusion, and 48h after MCAO. The effects of NBO treatment on lesion volumes, and CBF, ADC and T2 of ischemic core, perfusion-diffusion mismatch and normal tissue were analyzed longitudinally. The major findings were: i) NBO treatment was effective in both groups of stroke severities, salvaging similar percentage of initial abnormal ADC tissue, and ii) NBO treatments continued after reperfusion were more beneficial than NBO treatment during occlusion alone for both MCAO groups. These findings underscore the importance of the effects of NBO duration and stroke severity on treatment outcomes.