Astrocyte Regulation of Blood Flow in the Brain

Abstract

Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from active neurons evoke Ca 2þ increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K þ from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca 2þ signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow.A strocytes have an intimate relationship with blood vessels in the brain as their endfoot processes completely envelop all cerebral blood vessels. The interplay between astrocyte endfeet and the cerebral vasculature is an area of intense investigation as work over the past 10 years has shown that astrocytes are involved in the regulation of cerebral blood flow (CBF). Matching CBF to the metabolic demands of brain activity is essential for healthy brain function. The maintenance of brain homeostasis and cognitive processing requires substantial energy expenditures relative to the rest of the human body. It is estimated that 20% of total body energy consumption is caused by brain activity, although the brain represents only 2% of the total body weight. Calculations of the brain energy budget have estimated that the greatest proportion of the energy expenditure in the brain is attributed to synaptic transmission (Howarth et al. 2012). This suggests that synaptic transmission will be preferentially impacted by reductions in the energy supply to the brain. Oxidative metabolism in the brain is almost exclusively owing to aerobic glycolysis, indicating that glucose and oxygen are the primary energy fuels in the brain (Magistretti et al. 2000). Therefore, the roles of astrocytes in reg-

Poiseuille Flow of a Non-Local Non-Newtonian Fluid with Wall Slip: A First Step in Modeling Cerebral Microaneurysms

“…We notice that if α = 1, then Formula (26) reduces to (25). The slip condition (26) models the non-local entanglement and aggregation of the wall and fluid particles.…”

“…In Figure 1, we show a schematic of the structures that are involved in the formation of microaneurysms. A mathematical model capable of predicting the formation, growth and risk of rupture of a microaneurysm needs to incorporate the well-known non-Newtonian behavior of blood when flowing through smaller vessels [21,27,28], the deformability of the vascular wall [29] and relevant mechanotransduction processes taking place among red blood cells, endothelial cells and astrocytes [23,25]. The first step in building such a model is presented in this paper.…”

“…A chemo-mechanical entanglement of blood and endothelial cells at the blood-vascular wall interface that might be caused by a chemical imbalance and/or the forward and backward moving waves reflected from a bifurcation site [20] will cause slip of the blood at the wall. The slip will produce deviations from the expected shear stress level at the wall, which will make the red blood cells release the energy-making enzyme called ATP [21] that will activate a chemical response from the endothelial cells of the wall, which will lastly trigger neuronal-induced release of vasodilators from astrocytes whose endfeet continuously probe and control the amount of mechanical forces on the arterial wall and facilitate complex mechanotransduction processes [22][23][24][25][26]. According to [23,25], the two astrocyte endfeet use Ca 2+ -mediated chemical signals to control vasoconstriction (one endfoot) and vasodilation (the other endfoot).…”

Glial Contributions to Neural Function and Disease

“…Neuronal activity, reflected in the release of neurotransmitters from neurons, activates receptors on astrocytes. This in turn triggers a Ca 2ϩ response that is thought to promote release of vasoactive substances in the astrocytic endfeet that contact blood vessels (7,8). Astrocytes are proposed to not only promote increased blood flow and local oxygenation but also to take up glucose from the blood, convert it to lactate, and then release it to neurons for local energy use (9).…”

Evaluation of Wilson Disease With 18F-FDG PET/CT

“…There, it is almost entirely oxidized through sequential glycolysis and the tricarboxylic cycle associated with oxidative phosphorylation; and can also be stored as glycogen. Brain gray matter is responsible for the massive energy consumption [33 to 50 µmol ATP/g/min in neocortex) [22], most of it serves to restore the membrane gradient following neuronal depolarization, neurotransmitter recycling, intracellular signaling and dendritic and axonal transport. Glial and ependymal cells also have their own metabolic needs.…”