Molecular Markers of Neuroplasticity During Exercise in People With Incomplete Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional

Summary: 
      The purpose of this study is to determine whether exercising (walking) at different
      intensities increases levels of factors in the blood and saliva that are known to impact
      neuroplasticity (how the connections in the spinal cord and brain can change) and if these
      levels are changed by pairing exercise with a single dose of commonly used prescription drugs
      or by your mood.
    

Detailed description: 
      The protein brain-derived neurotrophic factor (BDNF) is known to promote cell survival,
      improve synaptic function, and induce neuronal morphological changes. Consequently, BDNF
      plays a major role in neuroplasticity and the ability of the central nervous system to adapt
      and recover following injury. Regardless of the molecular mechanisms by which this occurs
      (which are poorly understood), potentiating the expression of BDNF following spinal cord
      injury has been shown to improve functional outcomes in animals.(1, 2) It is well documented
      in both animal and human literature that the production BDNF increases with physical exercise
      in healthy populations and individuals with chronic disease or disability. (3) The literature
      suggests that this increase is proportional to the intensity of exercise, though the
      parameters of exercise to maximize this effect are poorly understood. (2, 4-6) From animal
      research, it has been postulated that serotonin (5HT) plays a role in the mechanism of
      increase in BDNF expression, (7-9) with findings that specifically demonstrate potentiation
      of the exercise-induced expression with antidepressant treatment(10)and a blunted response
      when monoaminergic signaling is blocked.(11) A specific genetic variation in the BDNF gene,
      found in approximately 30% of the population has also been noted as an important factor in
      the proper release of BDNF with associated deficits in motor learning. (12, 13) Initial
      evidence also suggests that this polymorphism may have an impact of the relationship between
      exercise and BDNF. (14, 15) The objective of this study is the evaluate the response of serum
      concentrations of brain-derived neurotrophic factor ([BDNF]s) to an acute bout of exercise in
      ambulatory people with incomplete spinal cord injury; additionally, to examine the effect of
      pharmacological agents that alter serotonergic (5HT) transmission on this exercise-induced
      change in [BDNF]s. To achieve this objective we will investigate [BDNF]s during a treadmill
      test alone and in combination with two commonly used medications; escitalopram oxalate , a
      selective-5HT reuptake inhibitor (SSRI) and cyproheptadine (CYPRO), a 5HT antagonist.

      Studies have also shown a relationship of BDNF to mood, in particular, depression. A
      secondary study will be performed in parallel with the primary study with the purpose of
      examining mood and how it correlates with the molecular markers for neuroplasticity as
      individuals participate in the repeated exercise and the other stated interventions. As the
      subjects progress over the course of the study time mood may change and may impact the
      relationship of the BDNF to the primary interventions.
    

Intervention name(s): escitalopram oxalate; Cyproheptadine; sugar pill; Graded intensity exercise
Intervention type(s): Drug; Drug; Drug; Other
Intervention description(s): 10 mg 4.5 hours prior to testing; 8mg 4.5 hours prior to testing; 4.5 hour prior to testing; modified bruce protocol for peak oxygen consumption testing
Other intervention name(s): Lexapro
Intervention MeSH terms: Cyproheptadine; Dexetimide; Citalopram; Escitalopram
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: BDNF; serotonin; high-intensity; exercise