Inhibition of sensory neuron apoptosis and prevention of loss by NT-3 administration following axotomy

Following permanent transection of their peripheral axons, a proportion of adult rat dorsal root ganglion neurons undergo programmed cell death (apopt osis) over a period of months. The underlying causes of this neuron loss ar e unclear, but may involve the interruption of the supply of target-derived neurotrophic factors, the replacement of which could prevent this loss fro m occurring. To investigate whether the administration of neurotrophic fact ors can prevent the dorsal root ganglion neuron death in adults, a 1 mg/ml solution of ciliary neurotrophic factor or of NT-3 was applied via a silico n reservoir to the proximal stump after unilateral sciatic transection at m id-thigh level. The incidence of apoptotic neurons and neuronal loss in the L4 and L5 ganglia ipsilateral to sciatic nerve transection when compared w ith the contralateral ganglia was then measured 1 month later. This was ass essed by examining serial sections of ganglia for neurons undergoing apopto sis and expressing the total counted as a percentage of the total number of neurons estimated using a stereological neuron counting technique. Our res ults show that NT-3 administration significantly reduced the incidence of a poptotic neurons and prevented neuron loss, while CNTF had no effect on eit her parameter. (C) 1999 Academic Press.