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With contemporary lifestyle changes and global aging, it is important yet unknown how stress interacts to post-stroke outcomes. This proposal aims to study the link between the stress-responsive FKBP51-related pathways and neural plasticity after stroke, elucidating FKBP5 gene polymorphisms and blood FKBP51 regulation in relation to brain excitability and functions, understanding the effects of transcranial direct current stimulation, and characterizing brain mechanisms for individualized early rehabilitation after stroke.
Stress is an underestimated risk factor and also a consequence of cardiovascular diseases and stroke. FK506-binding protein 51 (FKBP51) modulates stress responses by acting as a co-chaperone that negatively regulates glucocorticoid receptor (GR) to cortisol binding and nuclear signaling. In an oxygen-glucose deprivation (OGD) model of acute mouse hippocampal slices, FKBP5 deletion reduced ischemic neuronal hyperexcitation, and cathodal electrical stimulation of OGD-injured wild-type decreased FKBP51 levels. However, clinical implications of FKBP5 polymorphisms and FKBP51 regulation in post-stroke outcomes and neuromodulation-induced plasticity are unknown. We aim to assess the link between FKBP5 polymorphisms and blood FKBP51 regulation after stroke, and their relationship with stroke phenotypes, brain connectivity and functional outcomes.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active transcranial direct current stimulation (tDCS) | Experimental | Weak direct currents with 2 mA are delivered 20 minutes per session (including 30s ramp-up and 30s ramp-down) during tailored upper extremity task practice. Total sessions are 20 over 10 days. |
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| Sham tDCS | Sham Comparator | The device is automatically shut down after 2-minute stimulation. Treatment sessions and frequency are the same as the Experimental arm. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bihemispheric tDCS | Device | The anode and cathode are placed over the ipsilesional and contralesional primary motor cortex (C3 or C4 based on 10-20 system), respectively. The size of the electrode is 5x5 cm. |
| Measure | Description | Time Frame |
|---|---|---|
| Fugl-Meyer Assessment of Upper Extremity, FMA-UE | Motor recovery of upper extremity poststroke | Change score from baseline (~10 days poststroke) to 90 days poststroke |
| Measure | Description | Time Frame |
|---|---|---|
| Action Research Arm Test, ARAT | Motor function of upper extremity poststroke | Change score from baseline (~10 days poststroke) to 90 days poststroke |
| Fugl-Meyer Assessment of Lower Extremity, FMA-LE |
| Measure | Description | Time Frame |
|---|---|---|
| Resting-state structural and functional connectivity by magnetic resonance imaging | Connectivity-level plasticity post-intervention/poststroke | Change score from baseline (~10 days poststroke) to 90 days poststroke |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| I-Hui Lee, MD, PhD | Contact | + 886-2-28712121 | 8109 | ihlee@vghtpe.gov.tw |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Taipei Veterans General Hospital | Recruiting | Taipei | 112 | Taiwan |
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| ID | Term |
|---|---|
| D020521 | Stroke |
| ID | Term |
|---|---|
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Anticipated 100 participants are assigned to the experimental or sham-controlled groups with an allocation rate of 1:1, for the clinical trial. In addition, another group of patients participates in the observational study (no intervention).
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Motor recovery of lower extremity poststroke
| Change score from baseline (~10 days poststroke) to 90 days poststroke |
| Perceived Stress Scale-10 | Stress level poststroke | Change score from baseline (~10 days poststroke) to 90 days poststroke |
| Protein and gene test | Protein expression poststroke and identifying genotypes of participants | Change score from baseline (~10 days poststroke) to 90 days poststroke |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |