Anatomical correlates of recovery in single pellet reaching in spinal cord injured rats

Abstract

Modeling spinal cord injury (SCI) in animals is challenging because an appropriate combination of lesion location, lesion severity and behavioral testing is essential to analyze recovery of motor function. For particular tests such as single pellet reaching, the contribution of individual descending tracts to recovery has been investigated using specific tract ablation or graded lesions. However, it has not been established whether single pellet reaching is sufficiently sensitive for assessing the efficacy of treatments for cervical SCI (e.g., one of the currently most successful treatment approaches: rehabilitative training). To address this issue, we trained adult rats in single pellet reaching before and after a cervical (C4) spinal lesion. Animals with lesions of increasing severity were grouped into categories based on damage to anatomical structures such as the corticospinal tract (CST) and the rubrospinal tract (RST), two descending motor tracts that have been implicated in fine motor control of the forelimb. We related lesion extent to spontaneous recovery and plasticity-promoting post injury training and found that reaching performance was not correlated with lesion size or the extent of CST or RST injury. Interestingly, the dorsolateral quadrant (DLQ) lesion category, in which the unilateral dorsal CST and most of the unilateral RST are lesioned, was the only category that showed a clear effect of plasticity-promoting treatment (i.e., training), indicating its usefulness as a lesion model for this testing paradigm. The DLQ lesion likely strikes a balance between tissue sparing and functional impairment and is, therefore, best suited to maximize the potential to observe treatment effects of plasticity-promoting treatments using single pellet reaching. Because of the specific lesion size that is necessary to observe treatment effects, the single pellet skilled reaching task can be considered a stringent behavioral test and therefore may be useful for predicting translational success of potential treatments. However, due to the variability in the success rate, the labor-intensive nature, and the limited usefulness to test functional outcome of a wide range of lesion severities, we are hesitant to continue to use single pellet reaching to assess the effectiveness of currently available treatments for cervical SCI.

Keywords: Animal model; BL; CNS; CST; Compensation; Corticospinal tract; DLQ; Grasping; RST; Rubrospinal tract; SCI; Spinal cord injury; baseline; central nervous system; corticospinal tract; dorsolateral quadrant; rubrospinal tract; spinal cord injury.