The rate of cerebral blood flow (CBF) is positively correlated with brain activity. This 'functional hyperaemia' is mediated by the coordinated action of various vasoactive agents — including ions that are associated with synaptic transmission and some neurotransmitters — on blood vessels.
The increases in CBF that are associated with neural activity are spatially restricted to the site of activity. Local interneurons and astrocytes are probably crucial to regulation of CBF at this level, producing and releasing vasoactive mediators.
Vasodilation of extracerebral arteries that supply the site of neural activity is probably achieved through the upstream transmission of vasoactive signals within the walls of blood vessels.
The 'neurovascular unit' — a functional entity comprising neurons, astrocytes, smooth muscle cells and endothelial cells — has a key role in the haemodynamic response to brain activity.
Disruption of this regulatory network occurs in response to brain injury; for example, during stroke. Evidence now indicates that cerebrovascular dysfunction is a feature of neurodegenerative disorders such as Alzheimer's disease.
Accumulation of amyloid β-peptide (Aβ) in brain is associated with neuronal death in Alzheimer's disease. Aβ induces dysfunction in all cell types of the neurovascular unit and interferes with the function of blood vessels. These effects are mediated through reactive oxygen species.
The structural and functional integrity of the brain depends on the delicate balance between substrate delivery through blood flow and energy demands imposed by neural activity. Complex cerebrovascular control mechanisms ensure that active brain regions receive an adequate amount of blood, but the nature of these mechanisms remains elusive. Recent findings implicate perivascular neurons, gliovascular interactions and intramural vascular signalling in the control of the cerebral microcirculation. Neurons, astrocytes and vascular cells seem to constitute a functional unit, the primary purpose of which is to maintain the homeostasis of the brain's microenvironment. Alterations of these vascular regulatory mechanisms lead to brain dysfunction and disease. The emerging view is that cerebrovascular dysregulation is a feature not only of cerebrovascular pathologies, such as stroke, but also of neurodegenerative conditions, such as Alzheimer's disease.
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Supported by grants from the National Institutes of Health. The author is the recipient of a Javits award from the National Institute of Neurological Disorders and Stroke. J. Victor and V. Pickel provided helpful comments. The work of many colleagues could not be cited because of space limitations.
The author declares no competing financial interests.
Rate-limiting enzyme for the synthesis of prostanoids from arachidonic acid.
- P450 EPOXYGENASE
Family of enzymes that synthesizes epoxyeicosatrienoic acids and hydroxyeicosatrienoic acids from arachidonic acid.
- CYCLIN D2
An enzyme that controls the cell cycle by activating cyclin-dependent kinases leading to phosphorylation of cell cycle regulatory proteins.
- STELLATE INTERNEURONS
Inhibitory interneurons located in the outer layer of the cerebellar cortex, or molecular layer.
Cyclooxygenase reaction products including prostaglandins and thromboxanes.
- SWEDISH MUTATION
Abnormality in the amyloid precursor protein gene that was discovered in a Swedish family that has an unusually high incidence of early-onset Alzheimer's disease.
- SCAVENGER RECEPTOR
Membrane glycoprotein that mediates the recognition and uptake of various negatively charged macromolecules.
An unnatural amino acid that is used experimentally to study protein structure and function.
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Iadecola, C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci 5, 347–360 (2004). https://doi.org/10.1038/nrn1387
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