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.

No abstract

No abstract

Neutralizing the myelin-associated growth inhibitor Nogo-A in adult spinal cord-injured rats can promote regeneration of injured and compensatory sprouting of uninjured axons. Nogo-A is present in humans, making its neutralization a possible novel treatment option for paraplegic patients. In this study we examined the effects of an extensively used anti-Nogo-A antibody (mAb IN-1) on the regenerative capabilities of lesioned corticospinal tract (CST) axons in a primate, the Marmoset monkey. Unilateral thoracic lesions of the CST were performed in six adult Marmosets, followed by the application of mAb IN-1 into the cerebrospinal fluid circulation by a graft of hybridoma cells. A unilateral injection of biotin dextran amine into the motor cortex was performed to analyse sprouting and regeneration of the lesioned axons. In the control antibody-treated animal CST fibers stopped rostral to the lesion site and often showed retraction bulbs. In contrast, in four out of five mAb IN-1-treated animals fine labeled neurites had grown into, through and around the lesion site. Thus, this study provides first anatomical evidence that in primates, the neutralization of the myelin-associated inhibitor Nogo-A results in increased regenerative sprouting and growth of lesioned spinal cord axons.