NEUROTROPHIN-3 PREVENTS DEATH OF AXOTOMIZED CLARKES NUCLEUS NEURONS IN ADULT-RAT

In the present investigation, we studied whether neurotrophin-3 (NT-3) contributes to the rescue of axotomized Clarke's nucleus (CN) neurons in adult rats. A significant !(24%) loss of CN neurons occurred at L- l ipsilateral to T-8 hemisection by 14 days, which reached 31% at 2 mo nths and then stabilized. Axotomized CN neurons had also atrophied by 14 days, but mean cell size did not decrease further. Animals that rec eived gelfoam soaked in ner-ve growth factor, brain derived neurotroph ic factor, or ciliary neurotrophic factor at the lesion site also show ed a 30% neuron loss at 2 months, and a 40% reduction in average cell area. Rats receiving NT-3 showed a 15% neuron loss, which was not impr oved by additional neurotrophins in combination with NT-3. None of the treatments prevented neuron atrophy. Bioassay of the gelfoam showed t hat NT-3 bioactivity remained at 5 days after surgery but not at 14 da ys. Additional rats with hemisections that received NT-3 continuously via mini-pump for 2 months showed a 15% neuron loss, the same as with NT-3 given via gelfoam. These results indicate that even limited expos ure of axotomized CN neurons to NT-3 produces permanent rescue of 50% of the neurons. The virtually complete rescue that we had previously o bserved with transplants of fetal central nervous system (CNS) tissues may, therefore, be due at least in part to NT-3, but the exogenous ad ministration of a single neurotrophic factor or a combination of neuro trophic factors is less effective than transplants in producing long-t erm survival of axotomized CNS neurons. (C) 1998 Wiley-Liss, Inc.