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Chapter 25 Summary

There are three types of repair in the adult nervous system, in addition to functional reorganization of surviving neurons and circuits following brain damage. The first and most effective is the regrowth of severed peripheral axons (usually via the peripheral nerve sheaths once occupied by their forerunners) and the reestablishment of sensory and motor synapses on muscles or other targets. During this regeneration, mature Schwann cells provide many of the molecules. The second, and far more limited, type of repair is local sprouting or longer extension of axons and dendrites at sites of traumatic damage or degenerative pathology in the brain or spinal cord. Major impediments to such local repair include the death of damaged neurons due to trophic deprivation or other stress; inhibition of nerve growth by cytokines released during the immune response to brain tissue damage; and the formation of a glial scar by extensive hypertrophy of existing glial cells plus limited proliferation of glia at the site of the injury. The pathologic assembly of glial cell bodies and processes into a scar erects an impenetrable barrier to axon growth. In addition, glia—especially oligodendroglia, which normally produce CNS myelin—produce molecules that inhibit axon growth and synapse formation during development. The third type of repair is the ongoing generation of new neurons in the adult brain. Although there is no evidence for wholesale replacement of neurons and circuits in most vertebrate brains, the capacity for more limited neuronal replacement exists in many species. In most mammals, the olfactory bulb and the hippocampus are sites of adult neurogenesis. In both brain regions, new neurons are generated by neural stem cells retained in specific restricted locations, or niches, in the adult brain. Many of the molecules that regulate the maintenance, proliferation, and differentiation of adult neural stem cells and their progeny are used for similar purposes for neural stem cells in the embryonic brain. The limited prospects of developing this capacity to generate new neurons as a strategy for repair following brain injury or degenerative disease continue to captivate the imagination of patients and their physicians and motivate the efforts of many neuroscientists.