Effect of Exercise Gene Expression and Histone Modifications in Patients With Hemiplegia

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.

• Neurophysiological Assessment [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• Spasticity Assessment [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• Functional independence scale (FIM) [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• Fugl Meyer Upper Extremity Evaluation Questionnaire [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• A Rasch-built measure of manual ability(ABILHAND) Stroke Hand Function Questionnaire [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• Stroke Impact Questionnaire [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]
• 10 meter walk test [Time frame: Baseline (pre-treatment) and 6 weeks (post-treatment)]