Validation of the Weight-Drop Contusion Model in Rats: A Comparative Study of Human Spinal Cord Injury

Abstract

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.

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

“…Damage to the adult human cervical spinal cord dorsal columns leads to sensory dysfunctions of the upper limbs as evidenced by transient exaggeration or abolishment of the cutaneous sensations of fine touch, vibration, and proprioception (for a review, see York, 1985;Nathan et al, 1986). Similarly (Metz et al, 2000;Norenberg et al, 2004), transient and persistent upper limb cutaneous sensation dysfunctions occur in adult rats with damage to their cervical spinal cord dorsal columns (Schrimsher and Reier, 1993;McKenna and Whishaw, 1999;Ballerman et al, 2001a,b;Onifer et al, 2005;Kanagal and Muir, 2007). Abolished upper limb somatosensory evoked potentials (SSEPs) also can recover spontaneously in persons with incomplete cervical SCI (Curt and Dietz, 1996).…”

Providing the clinical basis for new interventional therapies: refined diagnosis and assessment of recovery after spinal cord injury

“…Recently, electrophysiological, behavioural, and imaging studies have indicated that the rat represents a reasonable model related to human SCI. 24 Consequently, in the near future, new therapeutic approaches to induce some axonal regeneration as well as enhancement of compensatory nerve fibre growth may become available for the treatment of patients with SCI.…”

Progress in Spinal Cord Research - A refined strategy for the International Spinal Research Trust

“…157 ± 159 A recent study analyzed the degree to which adult rat contusion injuries could serve as a model for human SCI. 159 Morphological, electrophysiological and functional outcome measures were used to compare rats lesioned with the NYU impactor model and human patients with chronic SCI. In both rats and humans close correlations were observed between lesion length and spinal cord atrophy (assessed by magnetic resonance imaging), prolonged latencies and reduced amplitudes in motor and somatosensory evoked potentials and impaired locomotor capacity (assessed by the 21-point BBB scale).…”

“…While it is not possible to do tract-tracing experiments in patients, high resolution imaging techniques such as magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS) and positron emission tomography (PET), which have previously been applied to the brain, can in theory be applied to the spinal cord. Indeed, important strides have recently been made in spinal cord imaging with both PET 194 and MRI, 159 and eventually, an`integrated package' of baseline measurements of the state of spinal cord damage, synaptic connectivity and residual function should be assembled.…”