Reply: The underestimated effect of normobaric hyperoxia on cerebral blood flow and its relationship to neuroprotection

Sir,We thank Chazalviel et al. (2016) for their interest in our article (Ejaz et al. , 2016) showing near-complete protection against neuronal damage and sensorimotor deficit by normobaric hyperoxia (NBO) in a rat model of brief middle cerebral artery occlusion (MCAO). Chazalviel et al. raise interesting issues regarding potential interactions between NBO and tissue plasminogen activator (tPA). To summarize, they argue that the available data from thrombo-embolic stroke models suggest that NBO when administered before tPA facilitates the latter’s thrombolytic properties, in turn increasing the chance of reperfusion and improved cerebral blood flow (CBF). Chazalviel et al. go one step further by arguing that the beneficial effects of NBO in experimental stroke may be largely, if not solely, due to this effect on perfusion, rather than to the—admittedly modest—increase in arterial oxygen content.Although their point that NBO facilitates the thrombolytic effects of tPA is important and may account for the previously reported synergism of NBO and tPA in reducing infarct volume (Henninger et al. , 2009), we believe it unlikely this to be the sole mechanism underlying the beneficial effects of NBO, and believe the latter are at least in part due to improved arterial oxygen. Several lines of evidence support this view, as follows: