NT-3, BUT NOT BDNF, PREVENTS ATROPHY AND DEATH OF AXOTOMIZED SPINAL-CORD PROJECTION NEURONS

Following spinal cord injury, projection neurons are frequently axotom ized and many of the cells subsequently die. One goal in spinal injury research is to preserve damaged neurons so that ultimately they are a ccessible to regeneration-promoting strategies. Here we ask if neurotr ophin treatment can prevent atrophy and death of axotomized sensory pr ojection neurons. In adult rats, a hemisection was made in the thoraci c spinal cord and axotomized neurons were retrogradely labelled with F luoro-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 signif icant degeneration was observed over lime 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. H emisected rats were treated with either neurotrophin 3 (NT-3) or brain -derived neurotrophic factor (BDNF,12 mu g/day for each), or a vehicle solution, delivered continuously to the lesion site via an osmotic mi nipump. Treatment with NT-3, but not BDNF, completely reversed cell at rophy in three of the four cell populations and also induced a signifi cant 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 sh ould be responsive to both BDNF and NT-3, However, only NT-3 treatment was neuroprotective, indicating that BDNF may not have reached the ce ll bodies of injured neurons, These results demonstrate that NT-3 may be of benefit in preventing the secondary cell loss that occurs follow ing spinal injury.