During acute hypoxia, increases in cerebral blood flow maintain brain oxygen delivery. In vitro and in vivo experiments conducted in rodent models show that during hypoxia, cortical astrocytes produce the potent vasodilator nitric oxide (NO) via nitrite reduction in mitochondria. Inhibition of mitochondrial respiration mimics, but also occludes, the effect of hypoxia on NO production in astrocytes. Astrocytes display high expression of the molybdenum-cofactor-containing mitochondrial enzyme sulfite oxidase, which can catalyze nitrite reduction in hypoxia. Replacement of molybdenum with tungsten or knockdown of sulfite oxidase expression in astrocytes blocks hypoxia-induced NO production by these glial cells and reduces the cerebrovascular response to hypoxia. These data identify astrocyte mitochondria as brain oxygen sensors that regulate cerebral blood flow during hypoxia via release of nitric oxide. Methods to study cerebral perfusion and hypoxia in rodents will also be discussed, with a particular focus on the physiological interpretation of MRI methods.

SPEAKER BIOGRAPHY

Isabel undertook a PhD at the Centre for Advanced Biomedical Imaging (CABI) in UCL working with Jack Wells and Mark Lythgoe to use fMRI, arterial spin labelling and optogenetics to study brain blood flow. Next Isabel undertook a post-doctoral research position with Alexander Gourine at the Centre for Cardiovascular and Metabolic Neuroscience (CCMN) also at UCL. In 2021 Isabel relocated to Sheffield soon after the birth of her third child. In 2024 Isabel received a wellcome trust career development award to study the use of hyperpolarised xenon for non-invasive brain oximetry.