Abstract
Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life. In this study, we used a clinically relevant chronic cervical contusion to study the therapeutic efficacy of rehabilitation in forelimb functional recovery. Nude rats received a moderate C5 unilateral contusive injury and were then divided into two groups with or without Modified Montoya Staircase (MMS) rehabilitation. For the rehabilitation group, rats were trained 5 days a week starting at 8 weeks post-injury (PI) for 6 weeks. All rats were assessed for skilled forelimb functions with MMS test weekly and for untrained gross forelimb locomotion with grooming and horizontal ladder (HL) tests biweekly. Our results showed that MMS rehabilitation significantly increased the number of pellets taken at 13 and 14 weeks PI and the accuracy rates at 12 to 14 weeks PI. However, there were no significant differences in the grooming scores or the percentage of HL missteps at any time point. Histological analyses revealed that MMS rehabilitation significantly increased the number of serotonergic fibers and the amount of presynaptic terminals around motor neurons in the cervical ventral horns caudal to the injury and reduced glial fibrillary acidic protein (GFAP)-immunoreactive astrogliosis in spinal cords caudal to the lesion. This study shows that MMS rehabilitation can modify the injury environment, promote axonal sprouting and synaptic plasticity, and importantly, improve reaching and grasping functions in the forelimb, supporting the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI.
Highlights
Spinal cord injury (SCI), often caused by motor vehicle accidents, falls, violence, or sports and recreational injuries, is characterized by partial or total loss of motor and sensory functions below the level of the injury resulting in severe permanent disabilities dependent on the level and severity of the lesion (Armour et al, 2016; Loy and Bareyre, 2019)
The data suggest that task-specific Modified Montoya Staircase (MMS) rehabilitation could promote functional recovery in reaching and grasping of the forelimb and paw after chronic cervical spinal cord injury (SCI)
Our results show that the amount of serotonin fibers in the ventral horns caudal to the injury is significantly increased in the MMS rehabilitation group compared to the control group, which is consistent with previous studies showing that rehabilitation can promote plasticity of serotonergic axons after SCI (Liu et al, 2017)
Summary
Spinal cord injury (SCI), often caused by motor vehicle accidents, falls, violence, or sports and recreational injuries, is characterized by partial or total loss of motor and sensory functions below the level of the injury resulting in severe permanent disabilities dependent on the level and severity of the lesion (Armour et al, 2016; Loy and Bareyre, 2019). Different locomotor training approaches have been shown to improve recovery after SCI in a variety of animal injury models (Jakeman et al, 2011; Harkema et al, 2012; Rossignol et al, 2015; Sandrow-Feinberg and Houle, 2015; Torres-Espin et al, 2018) These approaches can be categorized into voluntary and forced training. Combinatorial treatments including treadmill rehabilitation and pharmacological and electrical modulations in the lumbar spinal cord are able to partially restore locomotion in completely transected rats (van den Brand et al, 2012) These experimental results are similar to ones from recent clinical trials for treadmill training with or without epidural simulation (Rejc et al, 2017a,b; Tse et al, 2018), suggesting that animal studies are able to provide very useful insights for designing rehabilitation treatments for SCI patients. We have attempted to fill these gaps by investigating whether rehabilitation with MMS would promote functional recovery of the forelimb after a chronic cervical contusion injury
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