Abstract
The neurovascular unit (NVU) is a conceptual framework that has been proposed to better explain the relationships between the neural cells and blood vessels in the human brain, focused mainly on the brain gray matter. The major components of the NVU are the neurons, astrocytes (astroglia), microvessels, pericytes, and microglia. In addition, we believe that oligodendrocytes should also be included as an indispensable component of the NVU in the white matter. Of all these components, astrocytes in particular have attracted the interest of researchers because of their unique anatomical location; these cells are interposed between the neurons and the microvessels of the brain. Their location suggests that astrocytes might regulate the cerebral blood flow (CBF) in response to neuronal activity, so as to ensure an adequate supply of glucose and oxygen to meet the metabolic demands of the neurons. In fact, the adult human brain, which accounts for only 2% of the entire body weight, consumes approximately 20–25% of the total amount of glucose and oxygen consumed by the whole body. The brain needs a continuous supply of these essential energy sources through the CBF, because there are practically no stores of glucose or oxygen in the brain; both acute and chronic cessation of CBF can adversely affect brain functions. In addition, another important putative function of the NVU is the elimination of heat and waste materials produced by neuronal activity. Recent evidence suggests that astrocytes play pivotal roles not only in supplying glucose, but also fatty acids and amino acids to neurons. Loss of astrocytic support can be expected to lead to malfunction of the NVU as a whole, which underlies numerous neurological disorders. In this review, we shall focus on historical and recent findings with regard to the metabolic contributions of astrocytes in the NVU.
Highlights
The neurovascular unit (NVU) is a conceptual framework proposed to explain brain functions in health and disease in terms of the interactions between the component cells and the microcirculation in the brain [1–5] (Figure 1)
The functional activity of the brain enhances its adenosine triphosphate (ATP) production to replenish the ATP consumed by the Na+,K+-ATPase during the process of restoring the ionic concentration gradient of the neurons in the region, which entails an increase in the local cerebral metabolic rate of glucose (CMRglc) and the local cerebral metabolic rate of oxygen (CMRO2)
They hypothesized that arachidonic acid (AA) is released from the plasma membrane, by the increase in intracellular Ca2+ and Ca2+-sensitive phospholipase A2 (PLA2) induced by metabotropic glutamate receptors (mGluRs) stimulation, and by diacylglycerol (DAG)-activated phospholipase activated by phospholipase C (PLC)-induced increase in DAG
Summary
The neurovascular unit (NVU) is a conceptual framework proposed to explain brain functions in health and disease in terms of the interactions between the component cells and the microcirculation in the brain [1–5] (Figure 1). The core function of the normal brain is information processing by neurons, which is based on the movements of multiple ions across the cells. Alterations of the CBF occur in response to changes in neuronal activities, and changes in vascular caliber are observed even at the capillary level [1–5,7,8]. In addition to pericyte regulation, the capillary bed size may be actively regulated by an increase or decrease in water content in the Virchow–Robin space [29–31], the space between the astrocytic end feet and the outer surfaces of the microvessels. Cells 2022, 11, 813 are not in direct contact with the neurons, neurons may receive the required oxygen and glucose for ATP production for Na+,K+-ATPase activity from astrocytes, probably in the form of a partial metabolite (i.e., lactate or ketone bodies) [19–21]. Oxygen and glucose diffusing into the extracellular fluid may be taken up directly by the neurons
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