Translational Challenges of Rat Models of Upper Extremity Dysfunction After Spinal Cord Injury

Abstract

There are approximately 17,500 new spinal cord injury (SCI) cases each year in the United States, with the majority of cases resulting from a traumatic injury. Damage to the spinal cord causes either temporary or permanent changes in sensorimotor function. Given that the majority of human SCIs occur in the cervical spinal level, the experimental animal models of forelimb dysfunction play a large role in the ability to translate basic science research to clinical application. However, the variation in the design of clinical and basic science studies of forelimb/upper extremity (UE) function prevents the ease of translation. This review provides an overview of experimental models of forelimb dysfunction used in SCI research with special emphasis on the rat model of SCI. The anatomical location and types of experimental cervical lesions, functional assessments, and rehabilitation strategies used in the basic science laboratory are reviewed. Finally, we discuss the challenges of translating animal models of forelimb dysfunction to the clinical SCI human population.

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

“…Mice with silenced ipsilateral cerebellospinal projection neurons took longer to touch the food pellet and failed to successfully grasp it. Rodent models have been extensively studied for reaching and grasping because of the many conserved movements and neuroanatomical substrates across species [64][65][66][67][68]. Forelimb behaviors are reliably measured in the laboratory using a combination of qualitative and quantitative assessments of reach-to-grasp pellet retrieval tasks [56,69], supination tasks [70], digit manipulation [71][72][73], and grooming behaviors [74].…”

When Spinal Neuromodulation Meets Sensorimotor Rehabilitation: Lessons Learned From Animal Models to Regain Manual Dexterity After a Spinal Cord Injury

“…Different specific motor tasks are being used to assess the animals skills and abilities, including (A) single pellet reaching and grasping, (B) reaching and grasping in a staircase, (C) grip strength, (D) reaching and grasping form a grid, (E) food manipulation, such as pasta or cereals, (F) rope pulling, (G) horizontal ladder, and (H) treadmill locomotion. ladder, single pellet retrieval, grip strength, rope pulling and food manipulation [for a detailed review see (30)] (Figure 2). Among them, reaching and grasping-based paradigms, including singlepellet reaching and grasping (SPRG) implemented by Whishaw (42), Montoya staircase pellet retrieval (43), or seed/pellet retrieval from a grid floor (44) are the main methods chosen for rehabilitative training after cervical SCI.…”

“…As observed in the clinical setting, poor patient enrolment can severely compromise the successful execution of any rehabilitation protocol (72), and even those carefully designed to take maximum profit from the rehabilitative training would turn out to be ineffective. Several strategies aimed to ensure the animal's engagement in training have been explored with favorable results, although some associated drawbacks should also be acknowledged (30,73).…”

“…Based on the accumulated experience from the clinical rehabilitation centers, animal studies are focused on identifying the mechanisms of recovery, testing the additive synergies with other interventions, and importantly, setting efficient training regimes for achieving consistent functional recovery. However, due to the variety of protocols tested, and the lack of methodological consensus, the optimal parameters still need to be defined ( 30 , 31 ). Nevertheless, some lessons have been learned, and it is becoming clear that factors such as timing and training intensity, or those limiting training enrolment, have a decisive impact on successful motor recovery and must be carefully considered.…”

“…The first challenge to face when designing a rehabilitative training program for improving upper limb motor control is deciding which task(s) should be trained. Forelimb motor function is assessed in rodents with cervical SCI through a variety of tests, including over-ground locomotion, horizontal ladder, single pellet retrieval, grip strength, rope pulling and food manipulation [for a detailed review see ( 30 )] ( Figure 2 ). Among them, reaching and grasping-based paradigms, including single-pellet reaching and grasping (SPRG) implemented by Whishaw ( 42 ), Montoya staircase pellet retrieval ( 43 ), or seed/pellet retrieval from a grid floor ( 44 ) are the main methods chosen for rehabilitative training after cervical SCI.…”