Neurovascular dysfunction leads to failure to meet neuronal energy needs, which leads to oxidative stress and eventual neuronal death. Pericytes play a crucial role in the formation and functionality of the selectively permeable space that is the blood–brain barrier (BBB), and BBB disruption is a classic marker of vascular dysfunction. The NVU consists of arterial/arteriolar vascular smooth-muscle cells (VMSCs), endothelial cells, neuroglia (notably astrocytes), and pericytes. The brain’s energy needs are mainly met by neurovascular regulation of cerebral blood flow (CBF) ( Roy and Sherrington, 1890 Duling and Berne, 1970), realized by the neurovascular unit (NVU). It also summarizes the biological basis for the vascular contribution to AD, and provides critical perspective on the choice of CVR-mapping techniques amongst frail populations. This review focuses on the use of MRI to map CVR, paying specific attention to recent developments in MRI methodology and on the emerging stimulus-free approaches to CVR mapping. CVR is a measure that is rooted in clinical practice, and as non-invasive CVR-mapping techniques become more widely available, routine CVR mapping may open up new avenues of investigation into the development of AD. As a result, neuroimaging studies of AD are increasingly aiming to incorporate vascular measures, exemplified by measures of cerebrovascular reactivity (CVR). However, there is growing recognition of the link between cerebrovascular dysfunction and AD, supported by continuous experimental evidence in the animal and human literature. 2Department of Medical Biophysics, University of Toronto, Toronto, ON, CanadaĪlzheimer’s disease (AD) is associated with well-established macrostructural and cellular markers, including localized brain atrophy and deposition of amyloid.1Rotman Research Institute, Baycrest, Toronto, ON, Canada.Compr Physiol 9:1101-1154, 2019.Ĭopyright © 2019 American Physiological Society. Finally, topical avenues for future research are proposed. Factors that influence cerebrovascular reactivity are discussed and the mechanisms and regulatory pathways mediating the exquisite sensitivity of the cerebral vasculature to changes in PaCO 2 are outlined. Cerebrovascular reactivity and regional flow distribution are described, with further consideration of how differences in reactivity of parallel networks can lead to the "steal" phenomenon. Following a brief summary of key historical events in the development of our understanding of cerebrovascular physiology and an overview of the measurement techniques to index CBF this review provides an in-depth description of CBF regulation in response to alterations in PaCO 2. Further, age and sex, as well as vascular pathologies are also important to consider. As changes in PaCO 2 do not typically occur in isolation, the integrative influence of physiological factors such as intracranial pressure, arterial oxygen content, cerebral perfusion pressure, and sympathetic nervous activity must be considered. Alterations in the responsiveness of the cerebral vasculature can be detected with carefully controlled stimulus-response paradigms and hold relevance for cerebrovascular risk in steno-occlusive disease. In awake and healthy humans, PaCO 2 is the most potent regulator of CBF, and even small fluctuations can result in large changes in CBF. Increases and decreases in the partial pressure of arterial carbon dioxide (PaCO 2 ) lead to robust and rapid increases and decreases in cerebral blood flow (CBF). Intact, coordinated, and precisely regulated cerebrovascular responses are required for the maintenance of cerebral metabolic homeostasis, adequate perfusion, oxygen delivery, and acid-base balance during deviations from homeostasis.
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