TRANSPLANTS OF NEURONAL AND GLIAL RESTRICTED PRECURSORS COMBINED WITH MOTOR TRAINING PROMOTE RECOVERY AFTER CERVICAL SPINAL CORD INJURY IN RATS (2006)

Purpose/Hypothesis: Cervical spinal cord injury results in specific deficits of limb function. In the rat, lesions to the rubrospinal tract impair forelimb function despite the presence of an intact corticospinal tract, making it a useful pathway to study. Both functional and anatomical recovery have been promoted by transplantation of neuronal and glial restricted precursors following thoracic injury and task-oriented practice is used clinically to maximize recovery of function. Terefore, we hypothesized that combination therapy will improve reach-to-grasp function to a greater extent than either treatment delivered separately. Number of Subjects: Twenty-two adult female Sprague-Dawley rats that demonstrate a preference to reach with their right forelimb for single pellets of food. Materials/Methods: All animals received a partial lesion to the right cervical spinal cord between the C3-4 dorsal roots. Ten animals received an injection of a liquid collagen matrix (Lesion Only) and 12 had an injection of neuronal- and glial-restricted precursor cells into the lesion. Starting 5–7 days post-lesion, the 12 animals that received the cells were housed in a multilevel cage environment that promoted climbing and foraging for food. Starting at 9 days post-lesion, these 12 animals also spent 20-min/day, 5 days/wk in a reaching trough apparatus that provided task-oriented practice by encouraging reaching by the impaired limb for food pellets (NRP/GRP-Motor Training). All animals were assessed pre-injury and during weeks 1 and 8 postoperatively on 2 reach-to-grasp tests (Single Pellet and Staircase Reaching). Forepaw kinematics were collected using high-speed digial video (500 fps) and tracking the digits and wrist to assess wrist velocity, digit abduction, forepaw pronation excursion, and digit path-length ratios. Results: NRP/GRP-Motor Training group achieved significant recovery of function in the Staircase Reaching test at week 8 of recovery (F(2,40) = 11.12; p <; 0.001). The difference in reach-to-grasp ability between groups was highlighted by the number of animals that could retrieve pellets beyond the first two steps of the staircase test: 10 of 12 animals in the NRP/GRP+Motor Training group versus 2 of 10 animals in the Lesion Only group. Analysis of individual kinematic elements from the Single Pellet Reaching task allows detailed quantitation of specific movements. Preliminary analysis of the kinematics suggests that the NRP/GRP-Motor Training group improved the efficiency of the paw movement by reducing the path-length ratio to pre-injury levels. Results from groups that receive NRP/GRP cells tranplants or Motor Training alone will be analyzed and reported. Conclusions: Combination therapy of NRP/GRP cell transplants and daily motor training improved reach-to-grasp function over controls in our animal model of incomplete spinal cord injury. Clinical Relevance: As treatment of neurological injuries with stem cell populations advances, interaction with rehabilitative techniques needs to be considered.