Synopsis
The brain has a high energy demand, but cannot store energy. Consequently, it requires an uninterrupted and tightly controlled influx of blood to function. Neurovascular coupling comprises all mechanisms that determine cerebral blood flow (CBF) regulation following neuronal activity. The neurovascular unit is highly complex, involving excitatory neurons, interneurons, components of blood vessel walls such as smooth muscle cells and pericytes, as well as perivascular cells such as astrocytes and macrophages. All these cells can release molecules that can lead to vasodilation or vasoconstriction, and thereby determine the CBF response that accompanies neuronal activity, and therefore hemodynamic imaging signals.
Target audience
Students and researchers interested in using imaging techniques based on neurovascular coupling.Objective
Improve interpretation of hemodynamic imaging techniques from an understanding of the underlying mechanisms of neurovascular coupling.Purpose
Understand the physiology of neurovascular coupling
Understand how neurovascular coupling relates to hemodynamic imaging and the interpretation of imaging signals
Neurovascular coupling
The brain has a high energy demand, but cannot store energy. Consequently, it requires an uninterrupted and tightly controlled influx of nutrients to function. Neuronal activity is thought to be mainly supported through oxidative glucose mechanism, so that regulation of nutrient delivery occurs through cerebral blood flow (CBF) regulation in the active region. Changes in CBF following activity are also necessary to clear potentially toxic by-products (Iadecola 2017). The mechanisms that determine blood flow regulation following neuronal activity are known under the umbrella term of neurovascular coupling.The neurovascular unit describes all the components that take part in this process. This construct is highly complex and variable across regions and along the vascular tree, involving excitatory neurons, interneurons, components of blood vessel walls such as smooth muscle cells and pericytes, as well as perivascular cells such as astrocytes and macrophages (Girouard and Iadecola 2006, Iadecola 2017). All these cells can release molecules that can lead to vasodilation or vasoconstriction, and thereby determine the CBF response that accompanies neuronal activity.Vasoactive agents
Although there is some limited evidence for metabolic feedback control of CBF during neuronal activity (Iadecola 2017, Hosford and Gourine 2019), neurovascular coupling is thought to be predominantly determined through feed-forward mechanisms triggered by neuronal activity (Girouard and Iadecola 2006, Iadecola 2017, Hosford and Gourine 2019). Many molecules known to affect arteriole dilation are released by neurons. These include nitrous oxide (NO), which is thought to be one of the main mechanisms regulating neurovascular coupling ( Hosford and Gourine 2019). A large number of other molecules are likely to be involved however, including vasodilatory molecules such as the prostaglandins, epoxyeicosatrienoic acids (EET), K+ and adenosine, and vasoconstrictive molecules such as neuropeptide Y (Dirnagl, Niwa et al. 1994, Girouard and Iadecola 2006, Lecrux and Hamel 2011, Mishra, Reynolds et al. 2016, Iadecola 2017, Hosford and Gourine 2019).Consequences for hemodynamic imaging
Because the brain is an avid consumer of oxygen and because the volume of fully oxygenated blood is increased locally following neuronal activity, imaging techniques sensitive to these hemodynamic changes can be interpreted as proxies for neuronal activity (Buxton 2010). However, the quantitative interpretation of these techniques requires an understanding of the relative contributions of the different components that they are sensitive to, as well as their biases. An incomplete understanding of signal contributions and biases are especially problematic when comparisons are made between groups with potentially different neurovascular coupling such as in aging and dementia (Girouard and Iadecola 2006).Acknowledgements
No acknowledgement found.References
Buxton, R. B. (2010). "Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolism." Front Neuroenergetics 2: 8.
Dirnagl, U., K. Niwa, U. Lindauer and A. Villringer (1994). "Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide." Am J Physiol 267(1 Pt 2): H296-301.
Girouard, H. and C. Iadecola (2006). "Neurovascular coupling in the normal brain and in hypertension, stroke, and Alzheimer disease." J Appl Physiol 100(1): 328-335.
Hosford, P. S. and A. V. Gourine (2019). "What is the key mediator of the neurovascular coupling response?" Neurosci Biobehav Rev 96: 174-181.
Iadecola, C. (2017). "The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease." Neuron 96(1): 17-42.
Lecrux, C. and E. Hamel (2011). "The neurovascular unit in brain function and disease." Acta Physiol (Oxf) 203(1): 47-59.
Mishra, A., J. P. Reynolds, Y. Chen, A. V. Gourine, D. A. Rusakov and D. Attwell (2016). "Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles." Nat Neurosci 19(12): 1619-1627.