FIG 1.

Experimental time line. (A) The surgical procedure took place on day 1. During the procedure, a complete SCI was performed at the thoracic level (T12). An intrathecal catheter was also implanted subdurally and fitted to a programmable microinfusion pump (iPrecio^©) to deliver drugs to the lumbar enlargement of the spinal cord. During the post-SCI recovery period (∼4 days), saline was continuously delivered at a steady flow rate (3 μL/h) to prevent blockage of the tip of the cannula. The iPrecio^© Management System calculates the time at which the reservoir needs to be emptied from saline and re-filled with drug so as to reach the tip of the cannula 30 min prior to the first rehabilitation session. The saline remaining in the reservoir was then replaced through the subcutaneous port with the vehicle (10% DMSO in saline) for SCI controls, VU0240551 (30 μM) or TrkB-IgG (10 μg/mL in phosphate-buffered saline). (B) The pumps were programmed on a variable 24-h delivery schedule. Delivery started 30 min before the exercise session at a flow rate of 16 μL/h for 30 min followed by a 4 μL/h maintenance dose during the 60-min training session. Drug delivery was tapered off during the remaining 22.5 h to 0.2 μL/h, the lowest delivery flow to prevent clogging of the catheter. (C) Exercised groups received a 60-min bicycling session during which the hindlimbs go through a complete range of motion at a rate of 45 rpm. Sedentary animals are also seated on the apparatus for 60 min. (D) Example of EMG activity recorded during cycling. DMSO, dimethyl sulfoxide; EMG, electromyogram; SCI, spinal cord injury.