Survival of chronically-injured neurons can be prolonged by treatment withneurotrophic factors

Axonal regeneration by chronically-injured supraspinal neurons can be enhan ced by neurotrophic factor treatment at the site of injury, although the nu mber of regenerating neurons decreases as the interval between spinal cord injury and treatment increases. This study investigated whether this declin e in regenerative response could be due to continued loss of neurons during the post-injury period. Adult rats received a cervical hemisection lesion and axotomized neurons were labeled by retrograde transport of True Blue fr om the lesion site. Animals were killed one, four or eight weeks after inju ry and surviving neurons (True Blue-labeled) were counted in the red nucleu s and lateral vestibular nucleus. The neuron number in the lateral vestibul ar nucleus was stable for eight weeks after spinal cord injury, while survi val in the red nucleus decreased by 25% between four and eight weeks. To te st how neurons respond to a second injury with or without trophic factor tr eatment, at four, eight, 14 or 22 weeks after injury the lesion cavity was enlarged by 0.5 mm in a rostral direction. Gel foam saturated with ciliary neurotrophic factor, brain-derived neurotrophic factor or basic fibroblast growth factor was placed into the cavity. Animals were killed four weeks la ter. Re-injury of the spinal cord caused a significant decrease in neuron s urvival in both the red nucleus and lateral vestibular nucleus, the effects of which were lessened by treatment with ciliary neurotrophic factor or br ain-derived neurotrophic factor for the red nucleus and with ciliary neurot rophic factor for the lateral vestibular nucleus, when re-injured at four o r eight weeks. Basic fibroblast growth factor did not affect neuron surviva l at any time post-injury. Ciliary neurotrophic factor was not effective wi th longer delays (14 or 22 weeks) between the initial injury and re-injury. These results indicate a delayed pattern of secondary neuronal cell loss af ter spinal cord injury that is exaggerated by re-injury, bur which can be a meliorated by treatment with neurotrophic factors. (C) 1999 IBRO. Published by Elsevier Science Ltd.