Change in Neuroplasticity-Related Proteins in Response to Acute Activity-Based Therapy in Persons With Spinal Cord Injury

Background:

Activity-based therapy (ABT) focuses on regaining motor and sensory function below the level of the lesion in persons with a spinal cord injury (SCI). This is accomplished through repetitive training of specific motor tasks. Research has shown that ABT may increase neuroplasticity in the rat and human spinal cord.

Objective:

The primary aim of this study was to examine acute alterations in neuroplasticity-related proteins during ABT in persons with SCI.

Methods:

Volunteers were current participants in an ABT program and consisted of 12 men and 3 women (age, 31.8 ± 10.9 years) with chronic SCI (injury duration, 63.9 ± 54.4 months). A single 2-hour bout of ABT consisted of standing load bearing, body weight-supported treadmill training, whole body vibration, and functional electrical stimulation. Blood samples were obtained at baseline and immediately after completion of each modality to determine serum levels of brain-derived neurotrophic factor (BDNF), prolactin, and cortisol.

Results:

One-way analysis of variance (ANOVA) with repeated measures was used to examine differences in proteins over time. Results revealed baseline levels of BDNF (2.37 ± 1.41 ng/mL) that were lower than previous research has demonstrated in persons with SCI. No change in BDNF or cortisol was found, although prolactin was significantly reduced in response to ABT.

Conclusion:

Despite the length of the bout, acute changes in BDNF were not observed. Whether different intensities or modalities of ABT may promote acute increases in serum BDNF in individuals with SCI remains to be determined and further study is merited.Key words: BDNF, cortisol, exercise, prolactin, rehabilitation, spinal cord injuryRecent research demonstrates that exercise after spinal cord injury (SCI) may increase neuroplasticity in the rat and cycling. Exercise-mediated alterations in BDNF seem to be intensity-dependent, as no change in BDNF was shown during mild exercise versus human spinal cord.^1,2 However, the mechanisms more intense workloads. In addition, prolactin explaining this neuroplasticity are still relatively unexplored. Data from animal studies suggest that neurotrophic factors released during exercise may be a contributing factor. One such protein is brain-derived neurotrophic factor (BDNF), which is found in the brain and periphery. It promotes synaptic plasticity and neuronal growth in noninjured animals and alters motoneuron survival in animals with SCI. Increased levels of BDNF were demonstrated in healthy adults exercising at 55% and 75% maximal workload (Wmax),⁹ as well as in individuals with multiple sclerosis performing 30 minutes of moderate has been identified as a possible mediator of neuroplasticity in the spinal cord as it serves as a marker of serotonergic activation during exercise.¹² In a previous study, prolactin was increased (P < .05) in response to time trial arm ergometry in SCI athletes, yet mild exercise did not induce changes in prolactin. Whether this discrepant response of prolactin to exercise occurs in other individuals with SCI remains to be determined.Exercise also tends to increase cortisol release that may impact neurogenesis via an inhibition of growth in the hippocampus and/or through regulation of BDNF. Nevertheless, it has been suggested that this enhanced stressor response may have little effect upon neuroplasticity; as no correlation has been revealed between BDNF and cortisol, further study is warranted.It is not known whether acute exercise induces significant changes in neurotrophins in men and women with SCI, as only one study has examined this issue. Rojas-Vega et al required previously trained elite male athletes (VO₂max = 34.5 mL/kg/ min) with SCI from T4-T12 to complete a 42-km hand-biking time trial during which blood samples were obtained to measure concentrations of BDNF, cortisol, and prolactin.¹³ Results demonstrated increased (P < .05) BDNF with initiation of exercise, although postexercise values were similar to baseline. Postexercise measures of cortisol and prolactin were also higher (P < .05) than baseline levels. The population that was studied is relatively unique and exercise performed is atypical of common practice in the rehabilitation of persons with SCI, so it remains to be determined whether similar acute increases in neurotrophins would be revealed in less active individuals completing different exercise modalities.Activity-based therapy (ABT) consisting of high-volume training focusing on the core and lower extremities has recently been identified as an effective technique to promote functional recovery in this population.^17–19 The primary aim of this study was to examine acute changes in BDNF, cortisol, and prolactin during a prolonged bout of ABT in men and women with SCI. Individual changes in these proteins were also examined to better understand how different rehabilitation modalities may affect neuroplasticity. These data have the potential to impact the neurorehabilitation of persons with SCI. It was hypothesized that exercise would elicit significant acute changes in BDNF and cortisol as previously demonstrated in this population.¹³