Ciliary Neurotrophic Factor Promotes the Survival of Spinal Sensory Neurons Following Axotomy but Not during the Period of Programmed Cell Death

We have examined the in vivo survival effect of ciliary neurotrophic factor (CNTF) on sensory, i.e., dorsal root ganglion (DRG) neurons during the period of naturally occurring (programmed) cell death and following axotomy in the developing chick and mouse. Administration of CNTF during the period of naturally occurring cell death, from Embryonic Day (E) 6 to E10 in the chick and E14 to E18 in the mouse, had no significant effect in preventing the death of DRG neurons in either species. Axotomy on E12 in the chick or on Postnatal Day (PN) 5 in the mouse resulted in a 60% and a 33% decrease, respectively, in ipsilateral DRG neuron numbers by E16 (chick) or by PN12 (mouse), when compared to contralateral controls. CNTF treatment prevented axotomy-induced cell death of DRG neurons in both the chick and mouse. Daily administration of CNTF following axotomy in E12 chicks significantly increased (72%) DRG neurons by E16. Similarly, CNTF completely rescued mouse DRG neurons from axotomy-induced death. These results show that although CNTF has no effect on naturally occurring death of chick or mouse sensory neurons, this agent has significant ability to rescue sensory neurons following axotomy. These findings suggest that CNTF may be an effective therapeutic agent for the prevention of injury-induced death of vertebrate sensory neurons.