ATTEMPTS TO FACILITATE DORSAL COLUMN AXONAL REGENERATION IN A NEONATAL SPINAL ENVIRONMENT

The response to injury of ascending collaterals of dorsal root axons w ithin the dorsal column (DC) was studied after neonatal spinal overhem isection (OH) made at different levels of the spinal cord. The transga nglionic tracer, cholera toxin conjugated to horseradish peroxidase, a nd the anterograde tracer, biotinylated dextran amine, were used to la bel dorsal root ganglion cells with peripheral axons contributing to t he sciatic nerve. There was no indication of a regenerative attempt by DC axons at acute survival times (3 days and later) after cervical in jury, replicating previous work done at chronic survival periods (Lahr and Stelzner [1990] J. Comp. Neurol. 293:377-398). There was also no evidence of DC regeneration after lumbar OH injury even though immunoh istochemical studies using the oligodendrocyte markers Rip and myelin basic protein showed few oligodendrocytes in the gracile fasciculus at lumbar levels at birth. Therefore, the lack of myelin in the dorsal f uniculus at lumbar levels does not enhance the growth of neonatally ax otomized DC axons. In addition, DC axons did not regenerate when prese nted with fetal spinal tissue implanted into thoracic OH lesions, even though positive control experiments showed that segmental dorsal root axons containing calcition gene-related peptide and corticospinal axo ns grew into these implants, replicating previous work of others. When a thoracic OH lesion, with or without a fetal spinal implant, was com bined with sciatic nerve injury to attempt to stimulate an intracellul ar regenerative response of DRG neurons, again, no evidence of DC axon al regeneration was detected. Quantitative studies of the L4 and L5 do rsal root ganglia (DRG) showed that OH injury did not result in DRG ne uronal loss. However, sciatic nerve injury did result in significant p ost-axotomy retrograde cell loss of DRG neurons, even in groups receiv ing thoracic embryonic spinal implants, and is one explanation for the minimal effect of sciatic nerve injury on DC regeneration. Although f etal tissue did not appear to rescue a significant number of DRG neuro ns, the quantitative analysis showed an enlargement of the largest cla ss of DRG neuron, the class that contributes to the DC projection, in all groups receiving fetal tissue implants. This apparent trophic effe ct did not affect DC regeneration or neuronal survival after periphera l axotomy. Further studies are needed to determine why DC axons do not regenerate in a neonatal spinal environment or within fetal tissue im plants, especially because previous work by others in both the develop ing and adult spinal cord shows that dorsal root axons will grow withi n the same type of fetal spinal implant. (C) 1996 Wiley-Liss, Inc.