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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
30
10 mg 4.5 hours prior to testing
8mg 4.5 hours prior to testing
4.5 hour prior to testing
Rehabiliation Institute of Chicago
Chicago, Illinois, United States
Change in blood serum concentration of neuroplastic proteins
During a graded treadmill test, 5mL of blood will be taken at each speed the subject is able to obtain before failure. 5mL of blood will also be taken immediately after completion of the treadmill test and every 10 minutes for up to 30 minutes after completion.
Time frame: assessed prior to, throughout, and following the duration of a graded exercise test, over an expected average of 2 hours
fastest possible walking velocity overground
Time frame: one time, baseline measure
Six Minute Walk Distance
Time frame: one time basline measurement
Volitional strength: Lower Extremity Motor Score
Time frame: one time baseline measure
Modified Ashworth Scale
Time frame: one time baseline measurement
Spinal Cord Assessment tool for Spasticity
Time frame: one time baseline measure
Measure of Community mobility
Time frame: Step activity monitor worn on lower extremity for 7 days
Sagittal plane kinematics of excursions of hip/knee/ankle
Time frame: continuous assessment for an average of ten minutes at each visit
Peak ambulation velocity
Time frame: One time measure at the end of each graded intensity treadmilll test
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modified bruce protocol for peak oxygen consumption testing
Oxygen consumption
Time frame: continuous assessment for an average of ten minutes at each visit
Heart Rate
Time frame: continuous assessment for an average of ten minutes at each visit
Rating of Perceived Exertion (Borg Scale)
Time frame: continuous assessment for an average of ten minutes at each visit