LONG-DISTANCE AXONAL GROWTH IN THE ADULT CENTRAL-NERVOUS-SYSTEM

Neuroblasts taken from the developing central nervous system (CNS) can survive and later develop in the lesioned brain of adult recipients. These implanted neuroblasts develop many normal morphological and functional characteristics and, experimentally, substitute for intrinsic neurons. The rat striato-nigral system has been used as a model in which to study the ability of fetal neuroblasts to restore lesioned connections and promote functional recovery in brain lesioned animals. Tissue was obtained from the striatum and substantia nigra region either from E14-15 rat or mouse fetuses, or from 6-8 week old human fetal brain fragments, and implanted into the striatum or substantia nigra of rats previously subjected to neurotoxic lesions at one site or the other. Implanted neurons established extensive and highly specific connections with host cells; and in turn, the striatal implants received connections from all major afferent systems that normally innervate the striatum. In fact, implanted human striatal and nigral neuroblasts showed a remarkable capacity to grow axons along major myelinated pathways and to reach distant target areas. Extensive axonal projections from striatal cells implanted into the lesioned striatum were seen along the internal capsule and the cerebral peduncle to the nigra and as far as the spinal cord (a distance of about 20 mm). From the human nigral cells implanted into the lesioned nigra, axons grew along the medial forebrain bundle and the internal capsule to reinnervate large parts of the striatal complex and parts of the frontal cortex (a distance of about 10 mm). These results show that implanted fetal neuroblasts have the capacity to reconstruct specific circuitry over long distances in the lesioned adult brain.