Being exposed to a hypoxic environment causes a desaturation in the arterial oxygen content. In response to this, breathing and heart rate will be enhanced, and vascular smooth muscle will relax facilitating vasodilation. Overall, this maintains the delivery of oxygen to the cerebral tissue to suffice metabolic demand, despite the prevailing hypoxic environment. Paradoxically, some regions of the brain display a reduced perfusion during hypoxia. Particularly the posterior cingulate cortex, a major node of the default mode network, has consistently shown a reduction in perfusion during hypoxia. Furthermore, during memory recall, a function this region is explicitly involved in, hypoxia reversed the task induced BOLD response within this region. The observations in both the resting and functional brain suggest that hypoxia reverses neurovascular coupling.
This thesis contains three experiments designed to measure the functional, metabolic, and vascular changes to hypoxia on a regional level within the brain. With the aim of elucidating whether or not there is alteration in neurovascular coupling.
We have shown that hyperventilation induced hypocapnia during hypoxia and the resulting state of tissue alkalosis does not drive the reduction in regional cerebral blood flow. Hypoxia negates the increase in posterior cingulate glutamate during task. It is believed this reflects a regional shift towards non-oxidative metabolism in the absence of sufficient regional cerebral blood flow to meet metabolic demands. Resting levels of the inhibitory neurotransmitter GABA, are increased within the posterior cingulate cortex during hypoxia. This is indicative of an increased inhibitory tone within the region. Taken together, the reductions in blood flow and markers of enhanced non-oxidative metabolism suggest there is a state of neurovascular uncoupling during hypoxia. An up-regulation of regional inhibition may be contributing to this, however, it is unclear if increased GABA concentrations is a cause or effect of neurovascular uncoupling during hypoxia; this hypothesis requires further investigation.
This thesis provides a comprehensive investigation of the vascular, metabolic and neuroactivity changes in the brain during hypoxic stress. It adds to the ever-expanding body of research that aims to understand the functioning of the brain in health, disease and during environmental extremes.