Effect of Exercise on Neuroplasticity-Related Gene Expression and Histone Modifications in Patients With Hemiplegia
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Ischemic Stroke, Acute
- Sponsor
- Afyonkarahisar Health Sciences University
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Genetic analyses
- Status
- Recruiting
- Last Updated
- 5 months ago
Overview
Brief Summary
The aim of this study is to demonstrate the effect of routine exercise program on neuroplasticity through histone acetylation and gene expression changes in acute stroke survivors from an epigenetic perspective and to investigate the correlation of epigenetic effects with its effects on motor function and quality of life.
Detailed Description
Stroke is one of the leading causes of disability worldwide. Hemiplegia is the name of the clinical condition that occurs after a stroke. It is the loss of strength in the arm, leg and sometimes the face on one side of the body. Rehabilitation is vital to minimize the sequelae after a stroke, and patients who undergo continuous professional and systematic rehabilitation after the acute phase tend to recover rapidly. An important therapeutic goal of motor recovery is to maximize neuronal plasticity and facilitate motor tasks through motor learning during therapeutic exercise in the neurorehabilitation of patients with motor dysfunction. In particular, intact motor-related regions of the brain are expected to compensate for the impaired neuronal systems. Therefore, therapeutic exercise is expected to compensate for the impaired neuronal system by altering the (cortical) neuronal network as well as the expression of postsynaptic receptors, presynaptic neurotransmitters, regeneration, modulation and synaptic formation at cortical synapses. Epigenetic mechanisms regulate gene transcription based on modifications of DNA promoter regions and histones in chromatin. Epigenetic mechanisms include various DNA and histone modifications (i.e., methylation and acetylation of DNA and histones). In particular, the acetylation level of specific lysine residues in histones is one of the most powerful epigenetic modifications and is essential for transcriptional regulation. Studies show that exercise reduces the expression and activity of HDACs and increases histone acetylation, upregulating the expression of genes important for neuroplasticity. Some genes associated with neuroplasticity are:Brain-Derived Neurotrophic Factor (BDNF) , Cyclic adenosine monophasphate Response Element-Binding Protein (CREB1), Growth Associated Protein 43 (GAP43), Neurotrophic Receptor Tyrosine Kinase 2 (NTRK2), Synapsin I (SYN1). Histone H3 Lysine 27 Acetylation (H3K27ac) plays a critical role in the epigenetic regulation of gene expression and is associated with processes such as neuroplasticity, memory, and learning. Various studies have shown that environmental factors such as exercise can increase H3K27ac levels and thus support neuroplasticity. In this study, participants with acute hemiplegia will be given the same routine rehabilitation program. Neuroplasticity-related gene expression and histone acetylation levels will be compared in venous blood taken from the patient before and after exercise. In addition, the patient will be examined before and after exercise, and routine Mini-Mental Test, Brunnstrom, Fulg-Meyer upper and lower extremity evaluation, Spasticity evaluation with modified ashworth scale, Functional Independence Scale, ABILHAND Stroke Hand Function Questionnaire, Stroke Impact Questionnaire, 10-meter walking test will be performed to evaluate quality of life and motor function.
Investigators
Hasan Toktaş
Professor
Afyonkarahisar Health Sciences University
Eligibility Criteria
Inclusion Criteria
- •Participants who applied to Afyonkarahisar Health Sciences University Physical Therapy and Rehabilitation Clinic for rehabilitation purposes and had a stroke for the first time
- •Participants with ischemia as the etiology of stroke
- •Participants between the ages of 25-70
- •Drugs that have been used for at least 1 month and up to 6 months after a cerebrovascular accident
Exclusion Criteria
- •Participants whose stroke etiology is other than ischemia
- •Participants with clinically significant neurological disease other than stroke
- •Participants with systemic and musculoskeletal diseases that will not tolerate neurological rehabilitation and prevent them from participating
Outcomes
Primary Outcomes
Genetic analyses
Time Frame: Baseline (pre-treatment) and 6 weeks (post-treatment)
Real-Time Polymerase Chain Reaction (PCR) method will be used to determine the expression of BDNF, CREB1, GAP43, NTRK2 and SYN1 genes from the peripheral venous blood samples of the participants. The region of interest will be amplified in the Real-Time PCR device using primer pairs specific to the relevant genes. Changes in gene expressions in patients before and after treatment will be determined.
Histone Proteins
Time Frame: Baseline (pre-treatment) and 6 weeks (post-treatment)
Leukocytes will be isolated from blood samples before and after exercise. Isolation of histone proteins will be performed from the isolated leukocytes using the relevant isolation procedures. Pre- and post-treatment levels will be compared.
Histone Acetylation Analysis
Time Frame: Baseline (pre-treatment) and 6 weeks (post-treatment)
H3K27ac levels in the isolated histone proteins will be determined colorimetrically based on the ELISA method. Pre- and post-treatment levels will be compared.
Secondary Outcomes
- Neurophysiological Assessment(Baseline (pre-treatment) and 6 weeks (post-treatment))
- Spasticity Assessment(Baseline (pre-treatment) and 6 weeks (post-treatment))
- Functional independence scale (FIM)(Baseline (pre-treatment) and 6 weeks (post-treatment))
- Fugl Meyer Upper Extremity Evaluation Questionnaire(Baseline (pre-treatment) and 6 weeks (post-treatment))
- A Rasch-built measure of manual ability(ABILHAND) Stroke Hand Function Questionnaire(Baseline (pre-treatment) and 6 weeks (post-treatment))
- Stroke Impact Questionnaire(Baseline (pre-treatment) and 6 weeks (post-treatment))
- 10 meter walk test(Baseline (pre-treatment) and 6 weeks (post-treatment))