NT-3, but not BDNF, prevents atrophy and death of axotomized spinal cord projection neurons

Following spinal cord injury, projection neurons are frequently axotomized and many of the cells subsequently die. One goal in spinal injury research is to preserve damaged neurons so that ultimately they are accessible to regeneration-promoting strategies. Here we ask if neurotrophin treatment can prevent atrophy and death of axotomized sensory projection neurons. In adult rats, a hemisection was made in the thoracic spinal cord and axotomized neurons were retrogradely labelled with Fluoro-Gold. Four distinct populations of cells were identified in the lumbar spinal cord, and both numbers and sizes of labelled cells were assessed at different time points postlesion. A progressive and significant degeneration was observed over time with severe atrophy apparent in all cell populations and significant cell loss evident by 4 weeks postlesion. This time point was used to assess neurotrophin effects. Hemisected rats were treated with either neurotrophin 3 (NT-3) or brain-derived neurotrophic factor (BDNF, 12 microg/day for each), or a vehicle solution, delivered continuously to the lesion site via an osmotic minipump. Treatment with NT-3, but not BDNF, completely reversed cell atrophy in three of the four cell populations and also induced a significant increase in the number of surviving cells. In situ hybridization experiments showed trkB and trkC mRNA to be expressed in the majority of ascending spinal projection neurons, suggesting that these cells should be responsive to both BDNF and NT-3. However, only NT-3 treatment was neuroprotective, indicating that BDNF may not have reached the cell bodies of injured neurons. These results demonstrate that NT-3 may be of benefit in preventing the secondary cell loss that occurs following spinal injury.