## 4 Discussion  
To successfully evaluate potential experimental treatments for SCI, a suitable experimental animal, a valid injury model and reliable behavioral tests are required. Historically, researchers have used cats, dogs, and monkeys as experimental animals for in vivo SCI models [24; 25; 26; 27; 28]. However, several clinical trials based on these preclinical studies have failed because of the inconsistency of the animal models and assessment methods used [24; 25]. Since then, animal experiments have been relying on more standardized and reproducible species such as rats and mice. While mice are currently more suitable for transgenic technologies, allowing the exploration of underlying mechanisms of certain genes, the pathophysiological changes seen after SCI are more similar to humans in rats [29; 30; 31]. As an example, the development of a posttraumatic, intramedullary cyst is typically observed in humans and rats, but not in mice [32; 33]. Concerning the injury model, sharp injuries such as (hemi)-transections of the spinal cord have often been performed in preclinical animal experiments [34]. However, those injuries lead to substantially less inflammation, demyelination, gliotic scarring and neuron loss compared to the confusion-compression injury typically seen in human SCI [35]. Moreover, although the cervical spine, which is most commonly affected in human SCI, has a unique and complex cellular circuitry, injuries in animal models have predominantly been performed in the thoracic spine [12; 36]. Due to these considerations, clip confusion/compression injuries to the cervical spinal cord have been developed which are closer to reality in terms of their histological as well as clinical severity [10; 37]. For our current study, we, therefore, used a 28-g clip to induce an incomplete but severe cervical contusion/compression SCI at the C6 level in rats. As a result, the SCI animals showed quadriplegia immediately after the injury with most of them still being unable to bear their own weight one week later. Nevertheless, this combination of experimental animal and injury model/level used in our study, allowed for gradual recovery of motor  
Figure 9: Pearson correlation coefficients of all CatWalk \(\text{XT}^{\text{\tiny\textregistered}}\) parameters with the percentage of preserved tissue in SCI animals six weeks after the injury (N6). The \(r\) values and the respective CatWalk \(\text{XT}^{\text{\tiny\textregistered}}\) parameters are presented in a descending order from swing speed of the forelimbs (\(r\) = 0.98) to average speed (\(r\) = 0.33; \({}^{*}p\) \(<\) 0.05; \({}^{**}p\) \(<\) 0.01; \({}^{***}p\)\(<\) 0.001; classification of the correlation in red writing). function during the six weeks after SCI (N1-N6) and therefore can be seen as a suitable basis for behavioral testing and possibly the evaluation of potential experimental SCI treatments. Although neural regeneration within the adult spinal cord is generally limited after SCI, some extent of spontaneous sensorimotor recovery still occurs [38]. As the lesion in the spinal cord with its pathological changes is closer to the forelimb motor circuits in cervical SCI, this mechanism might contribute to the differences in spontaneous recovery between forelimbs and hindlimbs, observed by us and others [39; 40]: as depicted in Figures 2-5, all CatWalk \(\text{XT}^{\text{\tiny\textregistered}}\) parameters analyzed in our study showed a significant decrease (or increase in case of the base of support) from baseline to the first postinjury timepoint (N2) independent from the measured limbs. While gradual recovery over the following five weeks could then be observed for both, the hindlimbs and the forelimbs, the overall maximum level of spontaneous recovery was considerably higher in the hindlimbs compared to the forelimbs, with the most obvious differences in the parameters stride length (41.04% vs. 14.97%), print width (29.48% vs. 19.77%), and print area (24.83% vs. 12.46%).