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

Int J Mol Sci. 2021 May 4;22(9):4858. doi: 10.3390/ijms22094858.


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.

Keywords: BDNF; KCC2; chloride homeostasis; exercise; regeneration; rehabilitation; serotonin; spinal cord injury; sprouting.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Exercise*
  • Gene Expression Regulation*
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism
  • Humans
  • Nerve Regeneration / genetics*
  • Neuronal Plasticity / genetics*
  • Neurotrophin 3 / genetics
  • Neurotrophin 3 / metabolism
  • Quality of Life
  • Receptor, Serotonin, 5-HT2A / genetics
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Recovery of Function / genetics*
  • Serotonin / metabolism
  • Signal Transduction
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / genetics*
  • Spinal Cord Injuries / metabolism
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / rehabilitation
  • Symporters / genetics
  • Symporters / metabolism


  • Brain-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor
  • NTF3 protein, human
  • Neurotrophin 3
  • Receptor, Serotonin, 5-HT2A
  • SLC12A5 protein, human
  • Symporters
  • Serotonin
  • BDNF protein, human