Exercise-Induced Plasticity in Signaling Pathways Involved in Motor Recovery after Spinal Cord Injury

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.

Body Weight-Supported Treadmill Training Ameliorates Motoneuronal Hyperexcitability by Increasing GAD-65/67 and KCC2 Expression via TrkB Signaling in Rats with Incomplete Spinal Cord Injury

“…Both clinical and animal studies have found [ 10 , 17 – 20 ] that activity-based functional training can improve spasticity after SCI, and this effect may be associated with the increased synthesis of the tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF), GABA, and KCC2 in the spinal cord. Overexpression of BDNF in the damaged spinal cord increases the expression of glutamic acid decarboxylase 65/67 (GAD-65/67, the key enzymes in GABA synthesis), enhances inhibitory effects within the spinal cord, and promotes functional recovery in SCI rats [ 21 ].…”

“…The cyclic AMP response element-binding protein (CREB) and its phosphorylated counterpart (p-CREB) may involve in increasing GAD-65/67 expressions through regulating gene transcription downstream of TrkB signaling [ 10 ]. However, further investigations are required to determine whether exercise training can modulate the expression of GAD-65/67 and KCC2 in the distal of the spinal cord, enhance spinal inhibition, and improve spasticity via TrkB signaling after SCI.…”

Mitigating Gait Decline in a Woman With Parkinson’s Disease: A Case Report

“…Neuroplasticity refers to the capacity of the nervous system to modify itself in response to experience and injury [ 18 ]. Therefore, BDNF facilitates exercise-based recovery [ 19 ].…”

Treatment with Pulsed Extremely Low Frequency Electromagnetic Field (PELF-EMF) Exhibit Anti-Inflammatory and Neuroprotective Effect in Compression Spinal Cord Injury Model

“…To date, there is no FDA-approved treatment that can prevent the development of secondary SCI, nor one that induces regenerative processes [ 5 ]. Nonetheless, a moderate degree of functional recovery can be achieved using rehabilitative motor training [ 38 , 55 , 56 ]. Rehabilitation is probably one of the most important interventions following neurotrauma, and it can potentially improve a patient’s quality of life significantly.…”