Abstract
Few treatments for restoration of limb function after cervical SCI have made it to the clinical trial stage. In contrast, the literature is now replete with instances of significant functional improvement having been observed in preclinical animal models of SCI. What is responsible for this failure to translate genuine progress at the level of laboratory research into options for patients? One explanation is that the behavioral assays being used may lack the precision necessary to identify the neural causes of behavioral change after injury. Human and rodent “reach-to-eat movements” share enough similarities that analyzing mouse forelimb reaching behavior may be a method of identifying clinically relevant treatments. However, the outcome measure that is most commonly used to assess recovery in the Single Pellet Retrieval Task (SPRT), percentage of pellets successfully retrieved, is unable to distinguish between restoration of pre-injury motor patterns and the use of compensatory movements. In addition, it has been shown that success rate in the SPRT is not directly sensitive to the degree of corticospinal tract or rubrospinal tract injury, limiting its utility in assessing repair.
We aimed to establish outcome measures for the SPRT that could be both readily adopted by other laboratories and capable of differentiating between genuine recovery and compensation after SCI. We built mouse compatible motorized pellet dispensers that can be made using commercially available 3D printers. Using a computer vision software package, DeepLabCut™, we were able to track features of the mouse forepaw during pellet retrieval. This more detailed assessment of reaching behavior allowed us to compare post-injury kinematic changes and recovery of the ability to successfully retrieve pellets. Interestingly, changes in pronation and paw trajectory were poorly correlated with functional recovery as measured by success percentage. These results suggest that binary success/fail outcome measures may primarily assess an animal's ability to compensate rather than a restoration of normal function.