Pleiotrophin and Rehabilitative Training Following Cervical Contusion Spinal Cord Injury in Adult Female Lewis Rats

STUDY PURPOSE: To test the capabilities of pleiotrophin (PTN) to promote forelimb motor recovery after a cervical contusion spinal cord injury (SCI) in adult rats and to evaluate PTN as a potential treatment in the clinic. DATA COLLECTED: Adult female Lewis rats (n = 24) were trained to perform single pellet reaching, grasping and retrieval (SPRGR) task prior to SCI to establish baseline performance and preferred paw. Using a clinically relevant SCI model, a C5 lateral hemi-contusion injury was performed ipsilateral to the preferred paw, using an Infinite Horizons impactor. Immediately following SCI, PBS (1 µl per injection site; n = 12) or PTN (1.25 µg in 1 µl per injection site; n = 12) was injected into the intermediate gray matter (0.75 mm lateral of midline, 1.5 mm deep from surface), both ipsilesional and contralesional, and both 2.5 mm rostral and 2.5 mm caudal to the SCI site (i.e., 4 injections total).

Animals received SPRGR rehabilitative training starting a week after SCI. Training occurred 5 days/week for 10 min/day until the success rate of all rats plateaued (~6 weeks). The training was video recorded once per week and analyzed in a blinded manner.

Von Frey hair test was used to assess bilateral forepaw tactile sensitivity before and at 6 weeks post-SCI. Horizontal ladder task was used to assess limb function in a skilled locomotor task. All animals were video recorded on a horizontal ladder task prior to and at 2- and 6-weeks post-SCI and analyzed in a blinded manner.

Histological analysis of lesion severity was performed on transverse sections of the spinal cord showing the largest area of SCI damage. Sections were immuno-stained with 0.5% cresyl violet solution and visualized under brightfield and phase-contrast microscopy. DATA USAGE NOTES: