EFFECTS OF NERVE GROWTH-FACTOR, BRAIN-DERIVED NEUROTROPHIC FACTOR ANDNEUROTROPHIN-3 ON THE LAMINAR DISTRIBUTION OF TRANSGANGLIONICALLY TRANSPORTED CHOLERAGENOID IN THE SPINAL-CORD DORSAL HORN FOLLOWING TRANSECTION OF THE SCIATIC-NERVE IN THE ADULT-RAT

Spinal cord projections from transected sciatic nerves treated with di fferent neurotrophins were investigated in the adult rat following inj ections of choleragenoid into the proximal stump of the injured nerve. Transganglionically transported choleragenoid labelled primary affere nt fibres in all spinal cord dorsal horn laminae except the outer part of lamina II (IIo), which is almost devoid of labelling. Transection of the sciatic nerve, however, resulted in intense transganglionic cho leragenoid labelling in lamina IIo and in lamina I. In this study, the sciatic nerve was transected bilaterally and nerve growth factor (6 o r 24 mu g), brain-derived neurotrophic factor (20 mu g), neurotrophin- 3 (27 mu g) or cytochrome C (8 mu g; control substance) was applied un ilaterally during postoperative survival times of eight, 16 and 32 day s. The animals received bilateral injections of choleragenoid into the injured nerve two days before they were killed. The effect of the axo tomy and neurotrophin treatment was evaluated by analysing the extent of choleragenoid and substance P immunoreactivity in the somatotopical ly appropriate spinal cord dorsal horn regions. At eight days' postope rative survival, laminae I and IIo on the transected, non-treated side showed much more intense choleragenoid-like immunoreactivity compared to the contralateral transected, nerve growth factor-treated (6 and 2 4 mu g) side. A similar situation was also found in cases treated with the higher dose (24 mu g) at 16 days but to a lesser degree when the lower (6 mu g) dose was used. After 32 days' survival, there was no de tectable side difference in the choleragenoid labelling pattern. At 16 days' survival, the mean area of choleragenoid-positive ganglion cell body profiles in the L5 dorsal root ganglion of the transected, non-t reated side was significantly smaller than the mean area of the transe cted, nerve growth Factor-treated (24 mu g) neurons. An axotomy-induce d depletion of substance P-like immunoreactivity was seen from eight d ays' survival and onwards, whereas on the nerve growth factor-treated side a clearcut substance P depletion was not observed until 32 days. Brain-derived neurotrophic factor, neurotrophin-3 and cytochrome C had no detectable effects on the distribution of choleragenoid labelling or substance P-iike immunoreactivity in the dorsal horn Following scia tic nerve transection. In conclusion, peripheral nerve injury-induced expansion of primary afferent choleragenoid labelling in the spinal co rd dorsal horn is counteracted by treating the axotomized nerve with n erve growth factor. (C) 1997 IBRO.