GRAFTS OF FETAL CENTRAL-NERVOUS-SYSTEM TISSUE RESCUE AXOTOMIZED CLARKE NUCLEUS NEURONS IN ADULT AND NEONATAL OPERATES

Many conditions are thought to contribute to neuron death after axotom y, including immaturity of the cell at the time of injury, inability t o reestablish or maintain target contact, and dependence on trophic fa ctors produced by targets. Exogenous application of neurotrophic facto rs and transplants of peripheral nerve and embryonic central nervous s ystem (CNS) tissue temporarily rescue axotomized CNS neurons, but perm anent rescue may require transplants that are normal targets of the in jured neurons. We examined the requirements for survival of axotomized Clarke's nucleus (CN) neurons. Two months after hemisection of the sp inal cord at the T8 segment, there was an ipsilateral 30% loss of neur ons at the Ll segment in adult operates and a 40% loss in neonates. Tr ansplants of embryonic spinal cord, cerebellum, and neocortex inserted into the T8 segment at the time of hemisection prevented virtually al l of the cell death in both adults and neonates, but transplants of em bryonic striatum were ineffective. None of the grafts prevented the so mal atrophy of CN neurons caused by axotomy. Retrograde transport of f luoro-gold from the cerebellum demonstrated that 33% of all CN neurons at Ll project to the cerebellum, 50% of these died following a T8 hem isection, but all these projection neurons were rescued by a transplan t of embryonic spinal cord. These results suggest that the rescue of a xotomized CN neurons is relatively specific for the normal target area s of these neurons, but this specificity is not absolute and may depen d on the distribution and synthesis of particular neurotrophic agents. (C) Wiley-Liss, Inc.