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PLoS MEDICINE Hyperoxic Brain Effects Are Normalized by Addition of CO2 1 2 1* Paul M. Macey , Mary A. Woo , Ronald M. Harper 1 Department of Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America, 2 School of Nursing, University of California Los Angeles, Los Angeles, California, United States of America Funding: This work was supported A B S T R A C T by the National Institutes of Health Child Health and Human Development grant HD-22695. The study sponsor had no role in study Background design; collection, analysis, and interpretation of data; writing of the Hyperoxic ventilation (.21% O ) is widely used in medical practice for resuscitation, stroke 2 paper; or decision to submit for intervention, and chronic supplementation. However, despite the objective of improving tissue publication. oxygen delivery, hyperoxic ventilation can accentuate ischemia and impair that outcome. Competing Interests: The authors Hyperoxia results in, paradoxically, increased ventilation, which leads to hypocapnia, have declared that no competing diminishing cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces interests exist. other systemic changes, including increased plasma insulin and glucagon levels and reduced Academic Editor: Mervyn Singer, myocardial contractility and relaxation, which may derive partially from neurally mediated University College