Complete and Partial Lesions of the Pyramidal Tract in theRat Affect Qualitative Measures of Skilled Movements:Impairment in Fixations as a Model for Clumsy Behavior

Whishaw, Ian Q.; Piecharka, Dionne M.; Drever, Felicia R.

doi:10.1155/np.2003.77

Cited by 15 publications

(13 citation statements)

References 23 publications

(38 reference statements)

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“…CST injury causes distal impairments, with the hand more affected than the upper arm 16,35 . Indeed, the pellet reaching movements most perturbed by injury to pyramidal tract injury (supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Most people regain significant function after corticospinal injury, but rodent models often do not capture this recovery. This is perhaps because some rodent tasks are less reliant on CST and hence show minimal impairment postinjury, 16 while in other cases, it may be that they remain impaired following injury. 27 For example, the amount of recovery in stroke patients with usual care outstrips the effects of any current therapy.…”

Section: Discussionmentioning

confidence: 99%

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An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

Sindhurakar

Butensky

Meyers

et al. 2016

Neurorehabil Neural Repair

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Background. 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. Objective. To determine if quantification of forelimb supination in rats reveals large-scale functional loss and partial recovery after corticospinal injury. Methods. 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. Results. A cut lesion of the corticospinal tract produced a large deficit in supination. In contrast, there was no change in pellet retrieval success. Supination function recovered partially over 6 weeks after injury, and a large deficit remained. Motor cortex inactivation produced a dose-dependent loss of knob supination; the effect on pellet reaching was more subtle. Conclusions. The knob supination task reveals in rodents 3 signature hand function changes observed in humans with corticospinal injury: (1) large-scale loss with injury, (2) partial recovery in the weeks after injury, and (3) loss proportional to degree of dysfunction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

Sindhurakar

Butensky

Meyers

et al. 2016

Neurorehabil Neural Repair

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“…Both the horizontal ladder test and cylinder rearing are valuable assessments after cervical injury models. 8,9,10,11 The horizontal ladder test forces the animals to use both their injured and uninjured forelimbs to get across the ladder, and hence, the test measures the compensatory and adaptive function of the forelimb. During the pre-injury training, animals typically will "grab" or place their forepaw on the bars with their digits while crossing the ladder.…”

Section: Discussionmentioning

confidence: 99%

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

Lee

Streijger

Tigchelaar

et al. 2012

JoVE

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While the majority of human spinal cord injuries occur in the cervical spinal cord, the vast majority of laboratory research employs animal models of spinal cord injury (SCI) in which the thoracic spinal cord is injured. Additionally, because most human cord injuries occur as the result of blunt, non-penetrating trauma (e.g. motor vehicle accident, sporting injury) where the spinal cord is violently struck by displaced bone or soft tissues, the majority of SCI researchers are of the opinion that the most clinically relevant injury models are those in which the spinal cord is rapidly contused. 1 Therefore, an important step in the preclinical evaluation of novel treatments on their way to human translation is an assessment of their efficacy in a model of contusion SCI within the cervical spinal cord. Here, we describe the technical aspects and resultant anatomical and behavioral outcomes of an unilateral contusive model of cervical SCI that employs the Infinite Horizon spinal cord injury impactor.Sprague Dawley rats underwent a left-sided unilateral laminectomy at C5. To optimize the reproducibility of the biomechanical, functional, and histological outcomes of the injury model, we contused the spinal cords using an impact force of 150 kdyn, an impact trajectory of 22.5°(animals rotated at 22.5°), and an impact location off of midline of 1.4 mm. Functional recovery was assessed using the cylinder rearing test, horizontal ladder test, grooming test and modified Montoya's staircase test for up to 6 weeks, after which the spinal cords were evaluated histologically for white and grey matter sparing.The injury model presented here imparts consistent and reproducible biomechanical forces to the spinal cord, an important feature of any experimental SCI model. This results in discrete histological damage to the lateral half of the spinal cord which is largely contained to the ipsilateral side of injury. The injury is well tolerated by the animals, but does result in functional deficits of the forelimb that are significant and sustained in the weeks following injury. The cervical unilateral injury model presented here may be a resource to researchers who wish to evaluate potentially promising therapies prior to human translation. Video LinkThe video component of this article can be found at

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“…For qualitative assessment (accuracy) of the reaching and grasping task, we used a three point scoring system where 0 = absent, 0.5 = impaired or ambiguity regarding the movement, and 1 = normal (Whishaw et al, 2003; García-Alías et al, 2015). A total of seven components of the movement were analyzed: limb advance, digit extension, pronation (arpeggio), digit flexion, supination I, supination II, and pellet release.…”

Section: Methodsmentioning

confidence: 99%

Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats

Alam

García-Alías

Jin

et al. 2017

Experimental Neurology

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Enabling motor control by epidural electrical stimulation of the spinal cord is a promising therapeutic technique for the recovery of motor function after a spinal cord injury (SCI). Although epidural electrical stimulation has resulted in improvement in hindlimb motor function, it is unknown whether it has any therapeutic benefit for improving forelimb fine motor function after a cervical SCI. We tested whether trains of pulses delivered at spinal cord segments C6 and C8 would facilitate the recovery of forelimb fine motor control after a cervical SCI in rats. Rats were trained to reach and grasp sugar pellets. Immediately after a dorsal funiculus crush at C4, the rats showed significant deficits in forelimb fine motor control. The rats were tested to reach and grasp with and without cervical epidural stimulation for 10 weeks post-injury. To determine the best stimulation parameters to activate the cervical spinal networks involved in forelimb motor function, monopolar and bipolar currents were delivered at varying frequencies (20, 40, and 60 Hz) concomitant with the reaching and grasping task. We found that cervical epidural stimulation increased reaching and grasping success rates compared to the no stimulation condition. Bipolar stimulation (C6− C8+ and C6+ C8−) produced the largest spinal motor-evoked potentials (sMEPs) and resulted in higher reaching and grasping success rates compared with monopolar stimulation (C6− Ref+ and C8− Ref+). Forelimb performance was similar when tested at stimulation frequencies of 20, 40, and 60 Hz. We also found that the EMG activity in most forelimb muscles as well as the co-activation between flexor and extensor muscles increased post-injury. With epidural stimulation, however, this trend was reversed indicating that cervical epidural spinal cord stimulation has therapeutic potential for rehabilitation after a cervical SCI.

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Complete and Partial Lesions of the Pyramidal Tract in theRat Affect Qualitative Measures of Skilled Movements:Impairment in Fixations as a Model for Clumsy Behavior

Cited by 15 publications

References 23 publications

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

An Automated Test of Rat Forelimb Supination Quantifies Motor Function Loss and Recovery After Corticospinal Injury

A Contusive Model of Unilateral Cervical Spinal Cord Injury Using the Infinite Horizon Impactor

Electrical neuromodulation of the cervical spinal cord facilitates forelimb skilled function recovery in spinal cord injured rats

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