Neuroscience 6e Chapter 26 Summary

There are three types of cellular repair in the adult nervous system, in addition to the functional reorganization of surviving neurons and circuits that typically follows brain damage. The first and most effective is the regrowth of severed peripheral axons either from peripheral sensory neurons or central motor neurons, usually via the peripheral nerve sheaths once occupied by their forerunners. After regrowth, these axons reestablish sensory and motor synapses on muscles or other targets. During this regeneration, mature Schwann cells provide many of the molecules that regulate axon regrowth and targeting; these molecules are mostly those used for the same purpose during initial development. A 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 formation of glial scars; the death of damaged neurons due to trophic deprivation or other stress; inhibition of axon growth by protein components of myelin inhibition of neuronal 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 proliferation of glia at the site of the injury. The role of immune-mediated inflammation in establishing an anti-regenerative state in brain tissue is central. Molecular mediators of inflammation, including cytokines, their receptors, and related signaling intermediates, drive this process and establish barriers to neuronal regrowth. A third type of repair is 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 limited ongoing neuronal replacement exists in some species—sometimes in register with ongoing growth of the animal or due to seasonal variations. In most mammals, the olfactory bulb and the hippocampus are the only sites of adult neurogenesis. In both of these brain regions, new neurons are generated by neural stem cells retained in specific restricted locations 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 challenge of developing this capacity to generate new neurons and circuits as a strategy for repair following brain injury or degenerative disease continue to capture the imagination of patients, physicians, and many neuroscientists.