Mechanisms of Neuromuscular Fatigue Post Stroke
| Status: | Completed |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/21/2016 |
| Start Date: | August 2011 |
| End Date: | May 2015 |
While baseline weakness is clearly an important factor that contributes to disability post
stroke, neuromuscular fatigue (the acute reduction in force production) of the paretic
musculature likely compounds strength deficits and further exacerbates disability. The
proposed study aims to improve our understanding of the mechanisms of neuromuscular fatigue
in people post stroke in order to optimize strength training. In healthy individuals, both
central (neural) and peripheral (muscle) factors are determinants of neuromuscular fatigue,
but preliminary data from our laboratory suggests a greater contribution of central
components to neuromuscular fatigue in the paretic musculature. Although cortical pathways
are clearly disrupted post stroke, it is likely that brainstem pathways, known to have
neuromodulatory effects on spinal motor circuitry, are more involved in the sustaining of
force in the paretic leg, compared to the non-paretic and control legs. Therefore, the
purpose of this proposal is to examine the role of descending neuromodulatory pathways of
the brainstem in neuromuscular fatigue post stroke (Aim 1) and to correlate
brainstem-related changes in neuromuscular fatigue to walking function (Aim 2). The
investigators propose that stroke survivors' decreased capability to sustain force overtime
results from the diminished ability of spinal motoneurons to respond to brainstem
neuromodulatory inputs (serotonin (5-HT) and norepinephrine (NE)). Aim 1 will quantify
stroke-related decreases in motor output sensitivity to a 5-HT and NE reuptake inhibitor
(SNRI), serotonin antagonist, or placebo during sub-maximal intermittent fatiguing knee
extension contractions. If motoneurons are desensitized to descending monoamines in chronic
stroke patients, then they will be less sensitive to the effects of drugs that increase
monoamine levels. The investigators predict that in response to the SNRI or serotonin
antagonist, the paretic leg will show less change in time to task failure and a smaller
reduction in strength as compared to the non-paretic and control legs. For Aim 2, the
investigators predict that stroke subjects with the highest walking function will
demonstrate the greatest fatigue-related changes in response to the SNRI. This proposal
adopts an innovative model of motor impairment post stroke by including the role of
subcortical structures in neuromuscular fatigue.
stroke, neuromuscular fatigue (the acute reduction in force production) of the paretic
musculature likely compounds strength deficits and further exacerbates disability. The
proposed study aims to improve our understanding of the mechanisms of neuromuscular fatigue
in people post stroke in order to optimize strength training. In healthy individuals, both
central (neural) and peripheral (muscle) factors are determinants of neuromuscular fatigue,
but preliminary data from our laboratory suggests a greater contribution of central
components to neuromuscular fatigue in the paretic musculature. Although cortical pathways
are clearly disrupted post stroke, it is likely that brainstem pathways, known to have
neuromodulatory effects on spinal motor circuitry, are more involved in the sustaining of
force in the paretic leg, compared to the non-paretic and control legs. Therefore, the
purpose of this proposal is to examine the role of descending neuromodulatory pathways of
the brainstem in neuromuscular fatigue post stroke (Aim 1) and to correlate
brainstem-related changes in neuromuscular fatigue to walking function (Aim 2). The
investigators propose that stroke survivors' decreased capability to sustain force overtime
results from the diminished ability of spinal motoneurons to respond to brainstem
neuromodulatory inputs (serotonin (5-HT) and norepinephrine (NE)). Aim 1 will quantify
stroke-related decreases in motor output sensitivity to a 5-HT and NE reuptake inhibitor
(SNRI), serotonin antagonist, or placebo during sub-maximal intermittent fatiguing knee
extension contractions. If motoneurons are desensitized to descending monoamines in chronic
stroke patients, then they will be less sensitive to the effects of drugs that increase
monoamine levels. The investigators predict that in response to the SNRI or serotonin
antagonist, the paretic leg will show less change in time to task failure and a smaller
reduction in strength as compared to the non-paretic and control legs. For Aim 2, the
investigators predict that stroke subjects with the highest walking function will
demonstrate the greatest fatigue-related changes in response to the SNRI. This proposal
adopts an innovative model of motor impairment post stroke by including the role of
subcortical structures in neuromuscular fatigue.
Inclusion Criteria:
General
- be at least 18 years of age
- Cognitively able to give informed consent Stroke
-≥ 6 months post diagnosis of unilateral cortical stroke
- residual leg paresis
Exclusion Criteria:
General
- chronic low back or hip pain
- major psychiatric disorders (e.g. depression
- substance abuse
- head trauma
- neurodegenerative disorder
- any uncontrolled medical disorder (e.g. hypertension)
- taking any medication or supplement (e.g. St. John's Wort) that has 5-HT or NE
mechanisms of action(including Monoamine oxidase inhibitors (MAO) inhibitors)
- narrow angle glaucoma
- chronic liver or kidney disorders Stroke
- history of multiple strokes
- people who are unable to follow 2 step commands
- people who cannot walk ≥ 10 ft without physical assistance.
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