Neurotrophin-3 prevents death of axotomized Clarke's nucleus neurons in adult rat

Abstract

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-1 ipsilateral to T-8 hemisection by 14 days, which reached 31% at 2 months and then stabilized. Axotomized CN neurons had also atrophied by 14 days, but mean cell size did not decrease further. Animals that received gelfoam soaked in nerve growth factor, brain derived neurotrophic factor, or ciliary neurotrophic factor at the lesion site also showed 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 improved by additional neurotrophins in combination with NT-3. None of the treatments prevented neuron atrophy. Bioassay of the gelfoam showed that NT-3 bioactivity remained at 5 days after surgery but not at 14 days. 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 exposure of axotomized CN neurons to NT-3 produces permanent rescue of 50% of the neurons. The virtually complete rescue that we had previously observed with transplants of fetal central nervous system (CNS) tissues may, therefore, be due at least in part to NT-3, but the exogenous administration of a single neurotrophic factor or a combination of neurotrophic factors is less effective than transplants in producing long-term survival of axotomized CNS neurons.