Animal models are widely used for studying the pathophysiology as well as treatment strategies for injuries of the central nervous system. However, it is still unclear in how far the rat model of spinal cord injury (SCI) is valid for human SCI. Therefore, comparisons were made among functional, electrophysiological, and morphological outcome parameters following SCI in rats and humans. Contusion of the mid-thoracic spinal cord in 27 adult rats was induced by a weight-drop, leading to severe deficits in open field locomotion at a chronic stage. The data of 85 human patients with chronic SCI were collected and compared with the rat data. In electrophysiological recordings, prolonged latencies and reduced amplitudes in both motor evoked potentials (MEP) and somatosensory evoked potentials (SSEP) were closely correlated to the impairment of locomotor capacity of lower limbs in rats and humans. The morphological parameters assessed by high-resolution magnetic resonance imaging (MRI) in both species indicated that the lesion length and spinal cord atrophy were significantly related to the electrophysiological and functional outcome parameters. In rats, histological analysis was performed and showed, in addition to the MRI, a close relationship between spared white matter and locomotor capacity. Our results suggest an analogous relationship in rats and humans with respect to functional, electrophysiological, and morphological outcomes. Thus, the techniques for evaluating the extent and severity of SCI in humans and rats are of comparable value. This indicates that the rat can serve as an adequate animal model for research on functional and morphological changes after SCI and the effects of new treatment strategies.

The limited plastic and regenerative capabilities of axons in the adult mammalian CNS can be enhanced by the application of a monoclonal antibody (mAb), IN-1, raised against the myelin-associated neurite growth inhibitor Nogo-A. The aim of the present study was to investigate the effects of this treatment on the functional recovery of adult rats with a dorsal over-hemisection of the spinal cord. Directly after injury, half of the animals were implanted with mAb IN-1-secreting hybridoma cells, whereas the others received cells secreting a control antibody (anti-HRP). A broad spectrum of locomotor tests (open field locomotor) score, grid walk, misstep withdrawal response, narrow-beam crossing) was used to characterize locomotor recovery during the 5 weeks after the injury. In all behavioral tests, the recovery in the mAb IN-1-treated group was significantly augmented compared with the control antibody-treated rats. EMG recordings of flexor and extensor muscles during treadmill walking confirmed the improvement of the locomotor pattern in the mAb IN-1-treated rats; step-cycle duration, rhythmicity, and coupling of the hindlimbs were significantly improved. No differences between the two groups with regard to nociception were observed in the tail flick test 5 weeks after the operation. These results indicating improved functional recovery suggest that the increased plastic and regenerative capabilities of the CNS after Nogo-A neutralization result in a functionally meaningful rewiring of the motor systems.