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, NGF, 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 degrees) compared to control animals (36 -/+ 1 degrees) 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 controls (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 & 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.
Namiki
J
J
University of Toronto and Toronto Western Research Institute, Ontario, Canada.
Kojima
A
A
Tator
C H
CH
D000818:Animals; D001369:Axons / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes; D009043:Motor Activity / Q000187:drug effects; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020933:Neurotrophin 3 / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012012:Red Nucleus / Q000473:pathology; D013003:Somatosensory Cortex / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology*; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D019208:Brain-Derived Neurotrophic Factor; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D013266:Stilbamidines; D020932:Nerve Growth Factor