Nerve growth factor protects adult sensory neurons from cell death and atrophy caused by nerve injury

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Abstract
The reaction of dorsal root ganglia (DRG) neurons to axotomy and its alteration by locally supplied nerve growth factor (NGF) were examined in adult rats. Surgically implanted silicone chambers attached to the severed tip of the sciatic nerve acted as reservoirs capable of providing prolonged access of NGF to the site of injury. The time course of NGF activity within the chambers was determined by using the standard NGF chick DRG bioassay. The fluid from chambers filled with the NGF-saline solution maintained NGF activity for periods up to 6 weeks after implantation. By 9 weeks, however, the fluid from most chambers failed to show any NGF activity in the bioassay. Experiments were designed to compare the response in adult rats to injury of DRG neurons receiving chambers filled with either NGF-saline or with only saline. The total neuronal counts in the lumbar fourth and fifth DRG at 3 weeks and 6 weeks after sciatic nerve section showed 22% and 16% cell death, respectively, in those injured neurons receiving saline-filled chamber implants. The animals that received chamber implants which contained an NGF-saline solution showed no cell death in the ipsilateral DRG at either 3 or 6 weeks after injury. Morphometric analysis of injured DRG neurons showed evidence of atrophy in the injured neurons which did not receive NGF. The degree of atrophy among all cell sizes was significantly decreased in those injured neurons receiving NGF. At 3 weeks after section the mean volume of injured neurons not treated with NGF was decreased by 28% as compared with only a 13% decrease in neurons treated with NGF. Similar findings were noted in the 6-week studies. NGF treatment did not alter the incidence of classic changes of chromatolysis in the groups of injured neurons receiving either NGF-saline-filled chambers or only saline-filled chambers.