Use-dependent reorganization of spared and severed descending pathways after contusion SCI in rats

Résumé 0

Most spinal cord injuries (SCIs) in humans result from a blunt trauma to the spine leading to contusion of the spinal cord and half of these accidents lead to chronic paralysis below the level of injury. However, even in those paralyzed patients, histological analyses reveal a subset of spared descending fibers in the majority of cases (Kakulas, 1999; Norenberg et al., 2004). Severe contusion SCI in rats reproduces these anatomical and functional features. We assessed the effects of neuroprosthetic rehabilitation on recovery of voluntary locomotion using this model. Neuroprosthetic rehabilitation was recently introduced and tested on rats staggered hemisection SCI that interrupted all direct descending projections while leaving a gap of interconnected intact neural tissue. The therapy demonstrated unprecedented functional results with electrochemically-enabled restoration of voluntary movements, including walking, running and stair-climbing (van den Brand et al., 2012). In the case of contused SCI rats, neuroprosthetic rehabilitation led to an enhanced functional outcome including the ability to sustain voluntary walking in the absence of any enabling factor in half of the trained animals. In the present project, we aimed at characterizing the changes in corticospinal and reticulospinal pathways in trained rats that regained supraspinal control over their hindlimbs following neuroprosthetic rehabilitation and in non-trained rats. We show that the spared reticulospinal tract (ReST) underwent reorganization in response to neuroprosthetic rehabilitation below but not above the lesion level. Additionally, we found extensive spontaneous sprouting of the corticospinal tract (CST) above the lesion. These results, together with significant secondary damages and neuroprotection, highlight the mechanisms that are specifically related to recovery of voluntary locomotion in our clinically relevant contusion model.