Migrated fetal astrocytes modulate nerve growth factor expression in host nucleus gracilis of the medulla after grafting in third cervical hindlimb dorsal columns of the spinal cord.

Nerve growth factor (NGF) immunoreactivity in the nucleus gracilis of the medulla was quantitated for 90 days after aspiration of the C3 spinal hindlimb dorsal columns of 36 adult rats. Half the lesioned animals were a lesion-only group. The remaining lesioned animals received an immediate graft of two 1.0-mm pieces of 14 day gestation fetal rat cervical spinal cord (prelabeled with Phaseolus vulgaris leucoagglutinin) into the aspiration pocket (graft group). There were 3 normal controls. Groups of animals were analyzed at 7, 14, 21, 30, 60, and 90 days. At 90 days, NGF immunoreactivity was significantly elevated in the nucleus gracilis of lesion-only animals. This increase in NGF immunoreactivity was augmented in glial end-feet surrounding neurons and was also observed in the cytoplasm of astrocytes and some neurons. Previous experiments have shown that the cluster neurons of the nucleus gracilis undergo atrophy at this time with a concomitant decrease in hindlimb placement. NGF immunoreactivity (90 days) in grafted animals, however, was significantly less than in lesion-only animals (P < 0.05) but remained significantly elevated above control animals (P < 0.05). Unlike in lesion-only animals, there were no NGF positive neurons in the nucleus gracilis of grafted animals. Previous experiments have shown that astrocytes from fetal spinal cord grafts migrate to the nucleus gracilis, maintain cluster neuron cell size, and improve hindlimb placement at 90 days. The present data indicate that modulation of detrimental increases in NGF appeared to be a mechanism by which migrated fetal astrocytes can be used as a system for cell therapy.