FOR MUCH OF ITS HISTORY, NEUROLOGY has been a discipline of outstanding diagnostic rigor but little therapeutic efficacy. Simply put, neurologists have been renowned for their ability to localize lesions with great precision but until recently have had little to offer in terms of treatment. This situation is now changing.
Advances in our understanding of the structure, function, and chemistry of the brain’s neurons, glial cells, and synapses have led to new ideas for treatment. Many of these are now in clinical trials, and some are already available to patients. Developmental neuroscience is emerging as a major contributor to this sea change for three main reasons. First, efforts to preserve or replace neurons lost to damage or disease rely on recent advances in our understanding of the mechanisms that control the generation and death of nerve cells in embryos (Chapters 45 and 46). Second, efforts to improve the regeneration of neural pathways following injury draw heavily on what we have learned about the growth of axons and the formation of synapses (Chapters 47 and 48). Third, there is increasing evidence that some devastating brain disorders, such as autism and schizophrenia, are the result of disturbances in the formation of neural circuits in embryonic or early postnatal life. Accordingly, studies of normal development provide an essential foundation for discovering precisely what has gone wrong in disease.
In this chapter, we focus on the first two of these issues: how neuroscientists hope to augment the limited ability of neurons to recover normal function. We shall begin by describing how axons degenerate following the separation of the axon and its terminals from the cell body. The regeneration of severed axons is robust in the peripheral nervous system of mammals and in the central nervous system of lower vertebrates, but very poor in the central nervous system of mammals. Many investigators have sought the reasons for these differences in the hope that understanding them will lead to methods for augmenting recovery of the human brain and spinal cord following injury. Indeed, we shall see that several differences in regenerative capacity of mammalian neurons have been discovered, each of which has opened promising new approaches to therapy.
We shall then consider an even more dire consequence of neural injury: the death of neurons. The inability of the adult brain to form new neurons has been a central dogma of neuroscience since the pioneering neuroanatomist Santiago Ramón y Cajal asserted that in the injured central nervous system, “Everything may die, nothing may be regenerated.” This pessimistic view dominated neurology for most of the last century despite the fact that Ramón y Cajal added, “It is for the science of the future to change, if possible, this harsh decree.” Remarkably, in the past few decades, evidence has accumulated that neurogenesis does occur in certain regions of the adult mammalian brain. This discovery has helped ...