COMBINATION OF BDNF AND NT-3 PROMOTES SUPRASPINAL AXONAL REGENERATIONINTO SCHWANN-CELL GRAFTS IN ADULT-RAT THORACIC SPINAL-CORD

We previously demonstrated that Schwann cells (SCs) in semipermeable g uidance channels promote axonal regeneration in adult rat spinal cord transected at the mid-thoracic level. Propriospinal but not supraspina l axons grew into these channels. Here, we tested the ability of exoge nous brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3 ) to promote axonal regeneration in this novel model. The two neurotro phins were delivered simultaneously into the channel by an Alzet minip ump at a rate of 12 mu g/day for each neurotrophin for 14 of 30 days t ested; phosphate-buffered saline, the vehicle solution, was used as a control. Significantly more myelinated nerve fibers were present in SC /neurotrophin grafts than in SC/vehicle grafts (1523 +/- 292 vs 882 +/ - 287). In the graft, at least 5 mm from the rostral cord-graft interf ace, some nerve fibers were immunoreactive for serotonin, a neurotrans mitter specific to raphe-derived axons in rat spinal cord, Fast blue r etrograde tracing from SC/neurotrophin grafts revealed labeled neurons in 10 nuclei of the brain stem, 67% of these being in the lateral and spinal vestibular nuclei. The mean number of labeled brain stem neuro ns in the SC/neurotrophin group (92; n = 3) contrasted with the mean i n the SC/vehicle group (6; n = 4). Our results clearly demonstrate tha t BDNF and NT-3 infusion enhanced propriospinal axonal regeneration an d, more significantly, promoted axonal regeneration of specific distan t populations of brain stem neurons into grafts at the midthoracic lev el in adult rat spinal cord. (C) 1995 Academic Press, Inc.