Profiling locomotor recovery: comprehensive quantification of impairments after CNS damage in rodents

Abstract

Rodents are frequently used to model damage and diseases of the central nervous system (CNS) that lead to functional deficits. Impaired locomotor function is currently evaluated by using scoring systems or biomechanical measures. These methods often suffer from limitations such as subjectivity, nonlinearity and low sensitivity, or focus on a few very restricted aspects of movement. Thus, full quantitative profiles of motor deficits after CNS damage are lacking. Here we report the detailed characterization of locomotor impairments after applying common forms of CNS damage in rodents. We obtained many objective and quantitative readouts from rats with either spinal cord injuries or strokes and from transgenic mice (Epha4−/−) during skilled walking, overground walking, wading and swimming, resulting in model-specific locomotor profiles. Our testing and analysis method enables comprehensive assessment of locomotor function in rodents and has broad application in various fields of life science research.

Versatile robotic interface to evaluate, enable and train locomotion and balance after neuromotor disorders

“…Evaluation of locomotor function in animals often relies on visual scoring systems 17 or single-variable analyses 14 that not only lack objectivity but also fail to capture the multidimensional correlative structures of locomotor control strategies 18 . Here we combined robotically assisted evaluation tools with sophisticated neurobiomechanical and statistical analyses.…”

“…We injected a volume of 500 nl at a depth of 1.2 mm with a rate of 6 nl s -1 . After each injection, the needle was left in place for 3 min before it was carefully removed 14 . The extent and location of the lesions was verified postmortem.…”

“…A unilateral cortical stroke has limited impact on basic locomotion in rats, but behavioral observations have suggested deficits in balance control 14 . To demonstrate impairment of equilibrium after stroke, we exploited the capacity of the robot to superimpose any force at any time and in any actuated degree of freedom onto the zero-force control mode.…”

“…Rhythmic movements arrested instantly when the propulsive neuroprosthesis stopped translating the rat forward (Supplementary Video 4). Rats with unilateral cortical stroke show significant impairments in contralesional paw placement when crossing a horizontal ladder 14 (Fig. 3).…”

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

“…Tests include the skilled paw-reaching staircase task [44][45][46] , pasta handling [47] , single-pellet retrieval [48,49] , ladder walking [50,51] , skilled walking and swimming [52,53] .…”