Title Page
Contents
Abstract 8
I. INTRODUCTION 10
II. MATERIALS AND METHODS 16
1. Preparation of CORM-2-SLNs 16
2. Physicochemical Characterization of CORM-2-SLNs 17
3. CO Release from CORM-2-SLNs 18
4. BBB Cell Line Culture and Treatment 19
5. Surgical Methods and Moderate Static Compression Spinal Cord Injury 20
6. Experimental Design 22
7. Basso, Beattie, Bresnahan Score 23
8. Neuropathic Pain Test 24
9. Western Blot Analysis 25
10. Blood-Spinal Cord Barrier Permeability Evaluation 27
11. Immunocytochemistry (In Vitro) 28
12. Immunocytochemistry (In Vivo) 29
13. Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate Biotin Nick End Labeling Assay 31
14. Luxol Fast Blue and Hematoxylin-Eosin Staining 32
15. Statistical Analysis 33
III. RESULTS 34
1. Physicochemical Properties of CORM-2-SLNs 34
2. CO Release Measurement 35
3. CORM-2-SLNs Upregulated the Phosphorylation of AKT Pathway, Suppressed the Activated p38 Mitogen-Activated Protein Kinase Pathway, and Exhibited the Anti-inflammatory Effects Following SCI 36
4. CORM-2-SLNs Attenuate the Activation of Apoptotic Signaling Pathway After SCI 37
5. The CORM-2-SLNs Inhibit Loss of Tight Junction Proteins in Endothelial Cells and Prevent Blood-Spinal Cord Barrier Disruption After SCI 40
6. The CORM-2-SLNs Protect Endothelial Cells and Play Neuroprotective Role Following SCI 42
7. CORM-2-SLNs Prevents Glial Scar Formation, Reduces Lesion Volume, and Improves Neurological Outcomes Following SCI 44
IV. DISCUSSION 58
V. CONCLUSION 63
REFERENCES 64
ABSTRACT IN KOREAN 74
Figure 1. Schematic diagram showing heme oxygenase (HO) enzymatic activity. 14
Figure 2. (A) Chemical structure of CORM-2, (B) Diagrammatic illustration of... 15
Figure 3. Experimental design and Pharmacological Treatment 47
Figure 4. Anti-inflammatory effects of the CORM-2-solution (CORM-2-S) and... 48
Figure 5. CORM-2 solid lipid nanoparticles (CORM-2-SLNs) attenuate caspase-3... 49
Figure 6. CORM-2 solid lipid nanoparticles (CORM-2-SLNs) inhibit loss of... 51
Figure 7. CORM-2 solid lipid nanoparticles (CORM-2-SLNs) attenuate the... 53
Figure 8. CORM-2 solid lipid nanoparticles (CORM-2-SLNs) provide... 54
Figure 9. CORM-2 solid lipid nanoparticles (CORM-2-SLNs) inhibit activation... 56