Effect of brain-derived neurotrophic factor nerve growth factor and neurotrophin-3 on functional recovery and regeneration after spinal cord injury in adult rats

This study examined whether continuous intramedullary infusion of brain-derived neurotrophic factor (BDNF) nerve growth factor (NGF) or neurotrophin-3 (NT-3) had either an early neuroprotective effect or a delayed effect on regeneration after spinal cord injury (SCI) in adult rats. BDNF NF NT-3 or vehicle was infused at a rate of 625 ng/h into the SCI site at T3 through an implanted cannula attached to an osmotic pump. This infusion was maintained for 14 days after a 35-g clip compression injury. At 4 weeks after injury the axonal tracer fluorogold (FG) was introduced into the spinal cord caudal to the lesion and the animals sacrificed 3 days later following behavioral assessment. The inclined plane score was significantly higher in BDNF-treated animals (45 ±3°) compared to control animals (36 ± 1°) at 1 week after injury (p < 0.05) although the scores were not significantly different at later times. BDNF-treated animals also showed more FG-labeled cells in the red nucleus and sensorimotor cortex (1, 638 ± 350 and 124 ± 83 respectively) compared to controis (1, 228 ± 217 and 36 ± 15 respectively) and a lower percent cavitation at the injury site (21.4 ± 10.4%) compared to control animals (32.3 ± 11.7%). Invasion and proliferation of Schwann cells and formation of peripheral myelin were more prominent at the injury site in the BDNF-treated animals than in the other groups. These results indicate that continuous intramedullary infusion of BDNF provides neuroprotection and enhances some regenerative activity after SCI.