Recent studies indicate that the end feet of astrocytes also play an important role in maintaining water homeostasis in brain tissue. Water channels (aquaporin AQP4) are found in end foot processes in which water crosses the blood–brain barrier. In pathologic conditions such as brain edema, these channels play a key role in reestablishing osmotic equilibrium in the brain.
The midline structures bordering the third and fourth ventricles are unique areas of the brain that are outside the blood–brain barrier.
Some parts of the CNS, however, are not isolated from substances carried in the bloodstream. The barrier is ineffective or absent in the sites located along the third and fourth ventricles of the brain, which are collectively called circumventricular organs. Circumventricular organs include the pineal gland, median eminence, subfornical organ, area postrema, subcommissural organ, organum vasculosum of the lamina terminalis, and posterior lobe of the pituitary gland. These barrierdeficient areas are most likely involved in sampling of materials circulating in the blood that are normally excluded by the blood–brain barrier and then conveying information about these substances to the CNS. Circumventricular organs are important in regulating body fluid homeostasis and controlling neurosecretory activity of the nervous system. Some researchers describe them as “windows of the brain” within central neurohumoral system.
Neuronal injury induces a complex sequence of events termed axonal degeneration and neural regeneration. Neurons, Schwann cells, oligodendrocytes, macrophages, and microglia are involved in these responses. In contrast to the PNS, in which injured axons rapidly regenerate, axons severed in the CNS usually cannot regenerate. This striking difference is most likely related to the inability of oligodendrocytes and microglia cells to phagocytose myelin debris quickly and the restriction of large numbers of migrating macrophages by the blood–brain barrier. Because myelin debris contains several inhibitors of axon regeneration, its removal is essential to the regeneration progress.
The portion of a nerve fiber distal to a site of injury degenerates because of interrupted axonal transport.
Degeneration of an axon distal to a site of injury is called anterograde (Wallerian) degeneration (Fig. 12.33, a and b). The first sign of injury, which occurs 8–24 hours after the axon is damaged, is axonal swelling followed by its disintegration. This leads to breakdown of the axonal cytoskeleton. Microtubules, neurofilaments, and other cytoskeleton components are disassembled, resulting in the fragmentation of the axon. This process is known as granular disintegration of the axonal cytoskeleton. In the PNS, loss of axon contact causes dedifferentiation of Schwann cells and breakdown of the myelin sheath that enclosed the axon. Schwann cells downregulate  expression of myelin-specific proteins (see page 365) and at the same time upregulate and secrete several glial growth factors (GGFs), members of a family of axon-associated neuregulins and potent stimulators of proliferation. Under the influence of GGFs, Schwann cells divide and arrange themselves in a line along their external laminae. Since axonal processes distal to the site of injury have been by phagocytosis, the linear arrangement of the Schwann cells’ external laminae resembles a long tube with an empty lumen (Fig. 12.33b). In the CNS, oligodendrocyte survival is dependent on signals from axons. In contrast to Schwann cells, if oligodendrocytes lose contact with axons, they respond by  initiating apoptotic programmed cell death.
The most important cells in clearing myelin debris from the site of nerve injury are monocyte-derived macrophages.