Appendix D: The Blood–Brain Barrier, Choroid Plexus, and Cerebrospinal Fluid

Introduction

• The Blood–Brain Barrier Regulates the Interstitial Fluid in the Brain

  • Distinctive Properties of the Endothelial Cells of Brain Capillaries Account for the Blood–Brain Barrier

  • Tight Junctions Are a Major Feature of the Anatomical Blood–Brain Barrier Composition and Structure

  • The Blood–Brain Barrier Is Permeable in Three Ways

  • Endothelial Enzyme Systems Form a Metabolic Blood–Brain Barrier

  • Some Areas of the Brain Lack a Blood–Brain Barrier

  • Brain-Derived Signals Induce Endothelial Cells to Express a Blood–Brain Barrier

  • Diseases Can Alter the Blood–Brain Barrier

• Cerebrospinal Fluid Is Secreted by the Choroid Plexuses

  • Cerebrospinal Fluid Has Several Functions

  • Epithelial Cells of the Choroid Plexuses Account for the Blood–Cerebral Spinal Fluid Barrier

  • Choroid Plexuses Nurture the Developing Brain

  • Increased Intracranial Pressure May Harm the Brain

• Brain Edema Is an Increase in Brain Volume Because of Increased Water Content

• Hydrocephalus Is an Increase in Volume of Cerebral Ventricles

To function optimally, neurons of the central nervous system and their supporting glia require a highly specialized environment. The fluids that bathe the central nervous system's interstitial and cerebrospinal compartments are regulated by the blood–brain and blood–cerebrospinal fluid (CSF) barriers. Evidence for these barriers was first obtained in the 19th century when it was observed that acidic vital dyes stain the brain if the dye is injected into the cerebrospinal fluid but not if injected into the blood stream.

The interstitial fluid in the brain and the cere- brospinal fluid in the intraventricular and subarachnoid spaces are separately compartmentalized. Homeostasis of these fluid compartments and ultimately the intracellular compartment of brain cells is regulated to a great degree by the blood–brain and blood–CSF barriers (Figure D–1). Endothelial cells of the cerebral microvasculature form the blood–brain barrier that regulates the movement of molecules between the blood and interstitial fluid compartments. Epithelial cells of the choroid plexus produce the cerebrospinal fluid and regulate its composition.

These barriers exclude toxic substances and protect neurons from circulating neurotransmitters such as norepinephrine and glutamate, the blood levels of which can increase greatly after a meal or in response to stress. The selective exclusion by the blood–brain barrier results primarily from specialized anatomical properties of the endothelial cells that limit the passive diffusion of water-soluble substances from the blood into the interstitial and cerebrospinal fluid compartments. As a result, many metabolites required for brain growth and function must be transported selectively across the brain endothelial and choroid epithelial cell surfaces. Specific transporters deliver energy substrates, essential amino acids, and peptides to the brain and remove metabolites.

The Blood–Brain Barrier Regulates the Interstitial Fluid in the Brain