Multimodal cortical and subcortical exercise compared with treadmill training for spinal cord injury.

BACKGROUND AND PURPOSE: Spared fibers after spinal cord injury (SCI) tend to consist predominantly of subcortical circuits that are not under volitional (cortical) control. We aim to improve function after SCI by using targeted physical exercises designed to simultaneously stimulate cortical and spared subcortical neural circuits. METHODS: Participants with chronic motor-incomplete SCI enrolled in a single-center, prospective interventional crossover study. Participants underwent 48 sessions each of weight-supported robotic-assisted treadmill training and a novel combination of balance and fine hand exercises, in randomized order, with a 6-week washout period. Change post-intervention was measured for lower extremity motor score, soleus H-reflex facilitation; seated balance function; ambulation; spasticity; and pain. RESULTS: Only 9 of 21 enrolled participants completed both interventions. Thirteen participants completed at least one intervention. Although there were no statistically significant differences, multimodal training tended to increase short-interval H-reflex facilitation, whereas treadmill training tended to improve dynamic seated balance. DISCUSSION: The low number of participants who completed both phases of the crossover intervention limited the power of this study to detect significant effects. Other potential explanations for the lack of significant differences with multimodal training could include insufficient engagement of lower extremity motor cortex using skilled upper extremity exercises; and lack of skill transfer from upright postural stability during multimodal training to seated dynamic balance during testing. To our knowledge, this is the first published study to report seated posturography outcomes after rehabilitation interventions in individuals with SCI. CONCLUSION: In participants with chronic incomplete SCI, a novel mix of multimodal exercises incorporating balance exercises with skilled upper extremity exercises showed no benefit compared to an active control program of body weight-supported treadmill training. To improve participant retention in long-term rehabilitation studies, subsequent trials would benefit from a parallel group rather than crossover study design.

SOD1 Lysine 123 Acetylation in the Adult Central Nervous System.

Superoxide dismutase 1 (SOD1) knockout (Sod1-/-) mice exhibit an accelerated aging phenotype. In humans, SOD1 mutations are linked to familial amyotrophic lateral sclerosis (ALS), and post-translational modification (PTM) of wild-type SOD1 has been associated with sporadic ALS. Reversible acetylation regulates many enzymes and proteomic studies have identified SOD1 acetylation at lysine 123 (K123). The function and distribution of K123-acetylated SOD1 (Ac-K123 SOD1) in the nervous system is unknown. Here, we generated polyclonal rabbit antibodies against Ac-K123 SOD1. Sod1 deletion in Sod1-/- mice, K123 mutation or preabsorption with Ac-K123 peptide all abolished antibody binding. Using immunohistochemistry, we assessed Ac-K123 SOD1 distribution in the normal adult mouse nervous system. In the cerebellum, Ac-K123 SOD1 staining was prominent in cell bodies of the granular cell layer (GCL) and Purkinje cell dendrites and interneurons of the molecular cell layer. In the hippocampus, Ac-K123 SOD1 staining was strong in the fimbria, subiculum, pyramidal cells and Schaffer collateral fibers of the cornus ammonis field 1 (CA1) region and granule and neuronal progenitor cells of the dentate gyrus. In addition, labeling was observed in the choroid plexus (CP) and the ependyma of the brain ventricles and central canal of the spinal cord. In the olfactory bulb, Ac-K123 SOD1 staining was prominent in axons of sensory neurons, in cell bodies of interneurons and neurites of the mitral and tufted cells. In the retina, labeling was strong in the retinal ganglion cell layer (RGCL) and axons of retinal ganglion cells (RGCs), the inner nuclear layer (INL) and cone photoreceptors of the outer nuclear layer (ONL). In summary, our findings describe Ac-K123 SOD1 distribution to distinct regions and cell types of the normal nervous system.