Methods for Functional Assessment After C7 Spinal Cord Hemisection in the Rhesus Monkey

Abstract

Background Reliable outcome measures are essential for preclinical modeling of spinal cord injury (SCI) in primates. Measures need to be sensitive to both increases and decreases in function in order to demonstrate potential positive or negative effects of therapeutics. Objectives To develop behavioral tests and analyses to assess recovery of function after SCI in the nonhuman primate. Methods In all, 24 male rhesus macaques were subjected to complete C7 lateral hemisection. The authors scored recovery of function in an open field and during hand tasks in a restraining chair. In addition, EMG analyses were performed in the open field, during hand tasks, and while animals walked on a treadmill. Both control and treated monkeys that received candidate therapeutics were included in this report to determine whether the behavioral assays were capable of detecting changes in function over a wide range of outcomes. Results The behavioral assays are shown to be sensitive to detecting a wide range of motor functional outcomes after cervical hemisection in the nonhuman primate. Population curves on recovery of function were similar across the different tasks; in general, the population recovers to about 50% of baseline performance on measures of forelimb function. Conclusions The behavioral outcome measures that the authors developed in this preclinical nonhuman primate model of SCI can detect a broad range of motor recovery. A set of behavioral assays is an essential component of a model that will be used to test efficacies of translational candidate therapies for SCI.

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

“…We recently showed that the range of recovery observed after removal of all ascending and descending fibers on 1 side of the spinal cord is substantially less (i.e., there is less variability in post-lesion performance between subjects) than observed after subtotal hemisection lesions [43]. Nonetheless, some animals recover substantially after a complete hemisection.…”

“…Animals that displayed self-injury may have received gabapentin (15-60 mg/kg/day) and/or haloperidol (0.01-0.05 mg/kg/day) in an effort to prevent further skin damage. In general, animals recovered the ability to sit and mobilize quickly; by 4 days post-hemisection, 90% of the animals are able to sit unassisted, and by 7 days, 65% of the animals were able to sit more than 50% of the time [43]. Development of spasticity was monitored by assessing the right hand and arm using the Modified Ashworth Scale [44] while the animal was seated in a testing chair prior to initiation of functional training.…”

“…Locomotor and skilled hand function were evaluated when monkeys were walking on a treadmill, performing hand tasks in a restraining chair, and spontaneously moving in a large enclosed, yet open field [43]. Animals were trained, and baseline data was collected starting at 3 to 5 months before spinal cord hemisection.…”

“…Animals were trained, and baseline data was collected starting at 3 to 5 months before spinal cord hemisection. Details of these functional outcome tests have been recently published [43]. Briefly, after spinal cord hemisection, monkeys spent approximately 30 minutes 5 times per week in the open field, approximately 20 minutes 2 times per week on the treadmill (speeds of 0.45, 0.89, 1.34, and 1.79 ms −1 ), and 30 minutes 3 times per week in the restraining chair.…”

“…Overall, animals recover to approximately 50% of pre-hemisection baseline performance after a C7 hemisection. Detailed reports on recovery of function in this model have been published (Table 1) [18,43].…”