Robotic Rehabilitator of the Rodent Upper Extremity: A System and Method for Assessing and Training Forelimb Force Production after Neurological Injury (original) (raw)
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Experimental Neurology, 2004
A large proportion of spinal cord injuries (SCIs) in humans are at the cervical (C) level, but there are few tests to quantitatively assess forelimb motor function after cervical spinal cord injury in rodents. Here, we describe a simple and reliable technique for assessing forelimb grip strength over time. Female C57Bl/6 mice were trained on the Grip Strength Meter (GSM, TSE-Systems), then received a lateral hemisection of the spinal cord at level C5, C6, C7, or T1. Gripping ability by each forepaw was then tested for 4 weeks postinjury. Before injury, there was no significant difference in the force exerted by either forepaw. After hemisections at C5, C6, or C7, the forepaw ipsilateral to the injury was initially completely unable to grip (day 2 postinjury), and there was a slight transient decrease in the strength of the contralateral paw compared to presurgical levels. The ipsilateral forepaw exhibited no ability to grip until about 10-14 days postlesion, at which time grip reappeared and strength then recovered over a period of a few days to a level that was about 50% of preinjury levels. Grip strength was minimally and transiently affected by hemisection at T1. The grip strength analysis provides a convenient, quantitative measure of the loss and recovery of forelimb function after cervical injury.
Experimental Neurology, 2005
Approximately 50% of human spinal cord injuries (SCI) are at the cervical level, resulting in impairments in motor function of the upper extremity. Even modest recovery of upper extremity function could have an enormous impact on quality of life for quadriplegics. Thus, there is a critical need to develop experimental models for cervical SCI and techniques to assess deficits and recovery of forelimb motor function. Here, we analyze forelimb and forepaw motor function in rats after a lateral hemisection at C5 and assessed the relationship between the functional impairments and the extent of damage to one descending motor system, the corticospinal tract (CST). Female Sprague-Dawley rats were trained on various behavioral tasks that require the forelimb, including a task that measures gripping ability by the hand (as measured by a grip strength meter, GSM), a food reaching task, and horizontal rope walking. After 8 weeks of post-injury testing, the distribution of the CST was evaluated by injecting BDA into the sensorimotor cortex either ipsi-or contralateral to the cervical lesion. Complete unilateral hemisection injuries eliminated the ability to grip and caused severe impairments in food retrieval by the forepaw ipsilateral to the lesion. There was no indication of recovery in either task. In cases in which hemisections spared white matter near the midline, there was some recovery of forelimb motor function over time. Assessment of rope climbing ability revealed permanent impairments in forelimb use and deficits in hindlimb use and trunk stability. Sensory testing using a dynamic plantar aesthesiometer revealed that there was no increase in touch sensitivity in the affected forelimb. For the cases in which both histological and behavioral data were available, spared forelimb motor function was greatest in rats in which there was sparing of the dorsal CST. D
2019
To date, the aim of spinal cord injury (SCI) researches in animals is to find the most effective treatment method which can lead to faster recovery. In order to evaluate if the method is effective, robust functional assessments are crucial. From the past to present, indicators to observe the recovery of the motor function in rodent SCI models are using human observance or the Basso, Beattie, and Bresnahan score (BBB score), force detection, and imaging approaches. Nevertheless, these indicators do not meet some requirements for a severe full transection injury case. The goal of this project is to develop a novel force sensing system for measuring the ground reaction force of rats with severe SCI. In total, this system was tested with 12 spinalized rats. Following a full transection at the T9-T10 level of the spinal cord in rats with a 2mm gap, a nanofiber scaffold containing Neurotrophin-3 (NT-3), as previously described, was implanted [1]. After 12 weeks of rehabilitative training, results showed that rats that underwent rehabilitation were able to gradually exert more force as compared to rats that did not undergo rehabilitation. At Week 6, the ground reaction force recorded in rats with rehabilitation was 0.8 ± 0.1 N in left limb and 0.75 ± 0.14 N in right limb. On the other hand, rats without rehabilitation exerted 0.52 ± 0.06 N in left limb and 0.47 ± 0.09 N in right limb. At Week 12, the force recorded in rehabilitated rats increased to 1.43 ± 0.13 N in left limb and 1.28 ± 0.17 N in right limb whereas in rats without rehabilitation, the force recorded was only 0.74 ± 0.12 N in left limb and 0.54 ± 0.11 N in right limb. These results not only showed that rehabilitation enhanced recovery of motor function, but also demonstrated the viability of measuring the ground reaction force applied by the rats as an assessment for a full spinal cord transection injury model.
Objective clinical assessment of motor function after experimental spinal cord injury in the rat
Journal of Neurosurgery, 1977
✓ A new method was developed for the clinical assessment of motor function in rats after experimental spinal cord injury. The method consists of placing the animal on an inclined plane which can be adjusted to provide a slope of varying grade, and then assessing the maximum angle of the plane at which the animal can maintain its position without falling. The method was used to quantitate motor function in normal rats and in rats subjected to myelectomy, and consistently showed major differences between the two groups. The method has many positive features: the plane is easy to construct and of low cost; and the test is rapid, non-invasive, repeatable, and consistent.
Translational Challenges of Rat Models of Upper Extremity Dysfunction After Spinal Cord Injury
Topics in Spinal Cord Injury Rehabilitation, 2018
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.
Median and ulnar nerve injuries reduce volitional forelimb strength in rats
Muscle & Nerve, 2017
Introduction-Peripheral nerve injuries (PNI) are among the leading causes of physical disability in the United States. The majority of injuries occur in the upper extremities, and functional recovery is often limited. Robust animal models are critical first steps for developing effective therapies to restore function after PNI. Methods-We developed an automated behavioral assay that provides quantitative measurements of volitional forelimb strength in rats. Multiple forelimb PNI models involving the median and ulnar nerves were used to assess forelimb function for up to 13 weeks postinjury. Results-Despite multiple weeks of task-oriented training following injury, rats exhibit significant reductions in multiple quantitative parameters of forelimb function, including maximal pull force and speed of force generation. Conclusions-This study demonstrates that the isometric pull task is an effective method of evaluating forelimb function following PNI and may aid in development of therapeutic interventions to restore function.
Reaching training in rats with spinal cord injury promotes plasticity and task specific recovery
Brain, 2007
In the current study we examined the effects of training in adult rats with a cervical spinal cord injury (SCI). One group of rats received 6 weeks of training in a single pellet reaching task immediately after injury, while a second group did not receive training. Following this period changes in cortical levels of BDNF and GAP-43 were analysed in trained and untrained animals and in a group with training but no injury. In another group of rats, functional recovery was analysed in the reaching task and when walking on a horizontal ladder. Thereupon, the cortical forelimb area was electrophysiologically examined using micro-stimulation followed by tracing of the lesioned corticospinal tract (CST). We found that trained rats improved substantially in the reaching task, when compared to their untrained counterparts. Trained rats however, performed significantly worse with their injured forelimb when walking on a horizontal ladder. In parallel to the improved recovery in the trained task, we found that the cortical area where wrist movements could be evoked by micro-stimulation expanded in trained rats in comparison to both untrained and uninjured rats. Furthermore, collateral sprouting of lesioned CST fibres rostral to the injury was increased in trained rats. Post-injury training was also found to increase cortical levels of GAP-43 but not BDNF. In conclusion we show that training of a reaching task promotes recovery of the trained task following partial SCI by enhancing plasticity at various levels of the central nervous system (CNS), but may come at the cost of an untrained task. Abbreviations: SCI = spinal cord injury; CST = corticospinal tract; CNS = central nervous system; RST = rubrospinal tract; CPG = central pattern generator by guest on March 5, 2016 http://brain.oxfordjournals.org/ Downloaded from Brain (2007), 130, 2993^3003 J. Girgis et al. by guest on March 5, 2016 http://brain.oxfordjournals.org/ Downloaded from Reaching training in spinal cord injured rats Brain (2007), 130, 2993^3003 Reaching training in spinal cord injured rats Brain (2007), 130, 2993^3003 Reaching training in spinal cord injured rats Brain (2007), 130, 2993^3003 Reaching training in spinal cord injured rats Brain (2007), 130, 2993^3003 Reaching training in spinal cord injured rats Brain (2007), 130, 2993^3003
Neurorehabilitation and neural repair, 2017
Rodents are the primary animal model of corticospinal injury and repair, yet current behavioral tests do not show the large deficits after injury observed in humans. Forearm supination is critical for hand function and is highly impaired by corticospinal injury in both humans and rats. Current tests of rodent forelimb function do not measure this movement. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. We developed a knob supination device that quantifies supination using automated and objective methods. Rats in a reaching box have to grasp and turn a knob in supination in order to receive a food reward. Performance on this task and the single pellet reaching task were measured before and after 2 manipulations of the pyramidal tract: a cut lesion of 1 pyramid and inactivation of motor cortex using 2 different drug doses. A cut lesion of the corticospinal tract produced a large deficit...
The isometric pull task: A novel automated method for quantifying forelimb force generation in rats
Journal of Neuroscience Methods, 2013
h i g h l i g h t s We describe the isometric pull task, a novel fully automated method to measure forelimb strength and function in rats. Several parameters of forelimb strength and function are accurately analyzed. Ischemic lesions of primary motor cortex significantly decrease all measures of performance in this task. The isometric pull task will be useful in assessing function in multiple models of brain damage and motor dysfunction.
Frontiers in Neurology, 2020
Spinal cord injury research in experimental animals aims to define mechanisms of tissue damage and identify interventions that can be translated into effective clinical therapies. Highly reliable models of injury and outcome measurement are essential to achieve these aims and avoid problems with reproducibility. Functional scoring is a critical component of outcome assessment and is currently commonly focused on open field locomotion (the "BBB score"). Here we analyze variability of observed locomotor outcome after a highly regulated spinal cord contusion in a large group of rats that had not received any therapeutic intervention. Our data indicate that, despite tight regulation of the injury severity, there is considerable variability in open-field score of individual rats at 21 days after injury, when the group as a whole reaches a functional plateau. The bootstrapped reference interval (that defines boundaries that contain 95% scores in the population without regard for data distributional character) for the score at 21 days was calculated to range from 2.3 to 15.9 on the 22-point scale. Further analysis indicated that the mean day 21 score of random groups of 10 individuals drawn by bootstrap sampling from the whole study population varies between 9.5 and 13.5. Wide variability between individuals implies that detection of small magnitude group-level treatment effects will likely be unreliable, especially if using small experimental group sizes. To minimize this problem in intervention studies, consideration should be given to assessing treatment effects by comparing proportions of animals in comparator groups that attain pre-specified criterion scores.