Title Page
Contents
ABSTRACT IN KOREAN 10
Ⅰ. INTRODUCTION 12
Ⅱ. MATERIALS AND METHODS 17
2.1. Animals 17
2.2. Cell culture & cell treatment 17
2.3. treadmill 18
2.4. transient middle cerebral artery occlusion (tMCAO) 18
2.5. Neurological severity score (NSS) 19
2.6. Animal experimental design 20
2.7. Estimation of infarct volume by cresyl violet staining 20
2.8. Metabolomics and statistical analysis 21
2.9. Western blotting 22
2.10. Immunohistochemistry 23
2.11. Cell viability assay 23
2.12. Oxygen glucose deprivation (OGD) 24
2.13. Statistical analysis 24
Ⅲ. RESULTS 25
3.1. Preconditioning exercise improved infarction and improved neurological severity score after transient middle cerebral artery occlusion in young and aged mice 25
3.2. Metabolomic analysis in young and aged mice that was performed in preconditioning exercised young and aged mice after tMCAO 28
3.3. Comparison of metabolic profiles of preconditioning exercised young and aged mice after tMCAO 30
3.4. Preconditioning exercise enhanced synaptic plasticity after tMCAO in young and aged mice 32
3.5. Preconditioning exercise improved cellular senescence in young mice after tMCAO 37
3.6. Integrity of blood-brain barrier (BBB) was protected by preconditioning exercise in aged mice after tMCAO 42
3.7. Exercise mimics enhanced brain cell viability and survival in brain endothelial cell (bEnd.3) 44
Ⅳ. DISCUSSION 46
Ⅴ. REFERENCE 49
ABSTRACT 54
Figure 1. Effect of exercise on brain health 13
Figure 2. Metabolic pathway and relative contents after tMCAO in mice 15
Figure 3. Exercise-and Exercise Mimetics-Induced Muscle Remodeling 16
Figure 4. Experimental design 18
Figure 5. Preconditioning exercise reduced infarct volume and improved Neurological severity scores after transient middle cerebral artery in young... 27
Figure 6. Multivariate analysis after tMCAO preconditioning exercised young and aged mice 29
Figure 7. Alterations of plasma metabolome by exercise after tMCAO in young and aged group 31
Figure 8. Synapsin-1 and PSD-95 expression in brain samples of the young group after tMCAO 34
Figure 9. Synapsin-1 and PSD-95 expression in brain samples of the aged group after tMCAO. 36
Figure 10. The level of p16, p21, and p53 in the ipsil after tMCAO in the young group. 38
Figure 11. Cell cycle regulatory protein levels after tMCAO in the young group. 39
Figure 12. The levels of aging markers in ischemic brain tissue after tMCAO in aged mice. 40
Figure 13. Changes in the levels of cell cycle markers in ischemic brain tissue after tMCAO in aged mice. 41
Figure 14. Fibrinogen expression in the brain after ischemic stroke in the aged group 43
Figure 15. Cell viability in the endothelial cell (bEnd.3) 45
Figure 16. Overview of the effects of preconditioning exercise after tMCAO in young and aged mice 48