Plasticity and growth factors in injury response

The central nervous system (CNS) possesses a well‐known capacity for circuitry rearrangement, or “plasticity,” which is maintained throughout life. Two well‐studied categories of CNS plasticity are the circuitry rearrangement which occurs in response to injury and that which occurs in response to normal environmental stimuli. In an injury response, such as that which follows partial denervation of the hippocampus by unilateral removal of the entorhinal cortex, undamaged fibers in the denervated zone sprout and form new connections to replace lost synapses. In addition, rearrangement of circuitry also takes place in nondenervated zones which are functionally associated with the denervated circuitry. These observations indicate that the CNS is capable of major remodeling of neuronal circuitry, both in response to an injury as well as in the absence of a direct insult. Importantly, such plasticity reactions after injury appear to mediate recovery of lost function in hippocampal‐dependent learning. Plasticity can also occur in response to relatively subtle stimuli, such as are found in an enriched environment or with exercise. Even tightly structured repetitive exercise, such as wheel‐running by rats, drives plasticity responses in brain regions such as the hippocampus, cortex, and cerebellum. Plasticity in response to injury and environmentally driven plasticity share similar molecular features, such as activation of growth factors, suggesting that some molecular events and mechanisms driving circuitry remodeling are common to all forms of plasticity. In this review, these two categories of CNS plasticity are discussed, using in vivo models to illustrate remodeling occurring after damage, as well as environmentally driven plasticity. MRDD Research Reviews 1998; 4:223–230 © 1998 Wiley‐Liss, Inc.