Medical Physiology, 3rd Edition

CHAPTER 11. The Neuronal Microenvironment

Bruce R. Ransom

Extracellular fluid in the brain provides a highly regulated environment for central nervous system neurons

Everything that surrounds individual neurons can be considered part of the neuronal microenvironment. Technically, therefore, the neuronal microenvironment includes the extracellular fluid (ECF), capillaries, glial cells, and adjacent neurons. Although the term often is restricted to just the immediate ECF, the ECF cannot be meaningfully discussed in isolation because of its extensive interaction with brain capillaries, glial cells, and cerebrospinal fluid (CSF). How the microenvironment interacts with neurons and how the brain (used here synonymously with central nervous system, or CNS) stabilizes it to provide constancy for neuronal function are the subjects of this discussion.

The concentrations of solutes in brain extracellular fluid (BECF) fluctuate with neural activity, and conversely, changes in ECF composition can influence nerve cell behavior. Not surprisingly, therefore, the brain carefully controls the composition of this important compartment. It does so in three major ways: First, the brain uses the blood-brain barrier (BBB) to protect the BECF from fluctuations in blood composition. Second, the CSF, produced by choroid plexus epithelial cells, strongly influences the composition of the BECF. Third, the surrounding glial cells “condition” the BECF.

The brain is physically and metabolically fragile

The ratio of brain weight to body weight in humans is the highest in the animal kingdom. The average adult brain weight is ~1400 g in men and ~1300 g in women—approximately the same weight as the liver (see p. 944). This large and vital structure, which has the consistency of thick pudding, is protected from mechanical injury by a surrounding layer of bone and by the CSF in which it floats.

The brain is also metabolically fragile. This fragility arises from its high rate of energy consumption, absence of significant stored fuel in the form of glycogen (~5% of the amount in the liver), and rapid development of cellular damage when ATP is depleted. However, the brain is not the greediest of the body's organs; both the heart and kidney cortex have higher metabolic rates. Nevertheless, although it constitutes only 2% of the body by weight, the brain receives ~15% of resting blood flow and accounts for ~20% and 50% of total resting oxygen and glucose utilization, respectively. The brain's high metabolic demands arise from the need of its neurons to maintain the steep ion gradients on which neuronal excitability depends. In addition, neurons rapidly turn over their actin cytoskeleton. Neuroglial cells, the other major cells in the brain, also maintain steep transmembrane ion gradients. More than half of the energy consumed by the brain is directed to maintain ion gradients, primarily through operation of the Na-K pump (see pp. 115–117). An interruption of the continuous supply of oxygen or glucose to the brain results in rapid depletion of energy stores and disruption of ion gradients. Because of falling ATP levels in the brain, consciousness is lost within 10 seconds of a blockade in cerebral blood flow. Irreversible nerve cell injury can occur after only 5 to 10 minutes of interrupted blood flow.

Cerebrospinal Fluid

Brain Extracellular Space

The Blood-Brain Barrier

Glial Cells