Abstract
Spinal cord injury (SCI) leads to numerous chronic and debilitating functional deficits that greatly affect quality of life. While many pharmacological interventions have been explored, the current unsurpassed therapy for most SCI sequalae is exercise. Exercise has an expansive influence on peripheral health and function, and by activating the relevant neural pathways, exercise also ameliorates numerous disorders of the central nervous system (CNS). While the exact mechanisms by which this occurs are still being delineated, major strides have been made in the past decade to understand the molecular underpinnings of this essential treatment. Exercise rapidly and prominently affects dendritic sprouting, synaptic connections, neurotransmitter production and regulation, and ionic homeostasis, with recent literature implicating an exercise-induced increase in neurotrophins as the cornerstone that binds many of these effects together. The field encompasses vast complexity, and as the data accumulate, disentangling these molecular pathways and how they interact will facilitate the optimization of intervention strategies and improve quality of life for individuals affected by SCI. This review describes the known molecular effects of exercise and how they alter the CNS to pacify the injury environment, increase neuronal survival and regeneration, restore normal neural excitability, create new functional circuits, and ultimately improve motor function following SCI.
Highlights
In the United States alone, there are an estimated 300,000 people living with a spinal cord injury (SCI), with approximately 17,000 new cases arising each year [1]
Exercise-induced improvements in spasticity are mimicked by a single dose of a KCC2-enhancing compound in unexercised rats with Spinal cord injury (SCI) [126], and are eliminated when KCC2 activity is blocked during exercise [62]
While some studies have found exercise to increase the expression of the 5-HT2A R following SCI [35,87], whether this contributes to the upregulation of KCC2 in synergy with the brain-derived neurotrophic factor (BDNF) pathway remains to be determined
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Investigating activity-dependent plasticity in animal models is critical, to optimize rehabilitation programs in the clinic, and to identify potential pharmacological strategies These may be used either in place of exercise when it is not possible due to comorbidities or lack of access, or in conjunction with exercise to enhance functional improvements. There is abundant evidence that exercise facilitates motor recovery after SCI, but how an increase in physical activity leads to improvements in neurological function, especially in terms of molecular mechanisms that promote plasticity of the injured spinal cord, remains elusive. The current literature suggests that exercise can: (1) modify the injury environment; (2) promote axonal sprouting of local spinal networks and remaining descending axons; (3) promote synaptic and ionic plasticity; and, importantly, (4) improve motor functions in both the hindlimbs and forelimbs, validating the therapeutic potential of task-specific rehabilitation for functional recovery after chronic SCI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
