SPINAL-CORD TRANSECTION IN ADULT-RATS - EFFECTS OF LOCAL INFUSION OF NERVE GROWTH-FACTOR ON THE CORTICOSPINAL TRACT AXONS

THE SPINAL CORD of adult female rats was completely transected at the T8 level. Nerve growth factor (NGF) was administered at the lesion sit e via indwelling, implanted, osmotic minipumps. Purified NGF was suppl ied at doses of 100, 200, and 500 mug during a 30-day period. Control rats were treated with saline. At the end of the treatment, the proxim al stump of corticospinal tract axons in the spinal cord was labeled w ith anterograde transported horseradish peroxidase (HRP) injected into the sensorimotor cortex. In control rats, the corticospinal tract axo ns ended abruptly, proximal to the zone of maximal damage. Sterile swe llings developed at the axon tips, and no labeled axonal sprouts were apparent. On the contrary, in NGF-treated animals, the leading front o f the corticospinal tract axons showed a trend of approaching the zone of maximal damage following abnormal paths through the dorsal-injured white matter. Axonal sprouts were seen more proximally, traveling tow ard the transection site in aberrantly located dorsal paths, completel y outside the normal position of the corticospinal tract. NGF seems to partly restore the pattern of the regenerative behavior of the severe d corticospinal tract axons after spinal cord transection in newborn r ats, i.e., the induction of axonal sprouting in aberrantly located dor sal paths. An automated image analysis of the HRP reaction field close to the transection site demonstrated that the density of HRP-labeled axons in the corticospinal tract was significantly higher in the NGF-t reated rats than in the control rats. This higher-labeling intensity m ight be caused by the influence of NGF on the mechanisms of HRP transp ort and/or to an NGF promotion of axonal sprouting from the severed co rticospinal tract axons.