아주대학교

목차

I Introduction 1
1.Definition and epidemiology of intracerebral hemorrhage 1
1.1 Clinical manifestation and diagnosis 1
2. Pathophysiology 3
2.1 Primary Brain Injury 3
2.2 Secondary Brain Injury 3
2.3 Ferroptosis 4
2.4 Cellular and Extracellular Responses to Brain Injury 5
2.5 MMPs and BBB Disruption 7
2.6 Chronic Phase of Intracerebral Hemorrhage 7
3.Treatment and management of ICH 8
3.1 Emerging Preclinical novel Therapies for ICH 9
3.2 Hydrogel 9
4. Aim of this study 11
II Materials and Methods 12
1. Animals and surgical procedure 12
2.Hydrogel preparation and injection 14
3.Tissue processing and immunohistochemistry 14
4.Cresyl violet and Hematoxylin & Eosine staining 15
5.Image acquisition and analysis 16
6.Magnetic Resonance Imaging (MRI) 17
7.Behavioral study 17
7.1 Pellet retrieval test 17
7.2 Ladder rung test 19
7.3 Cylinder test 19
III Results 20
1.Temporal Evolution of the ICH Lesion 20
1.1 Histological Assessment (H&E) of Lesion and Cavity 20
1.2 Lesion 3D Volume Quantification 22
1.3 Ventricular Enlargement Following ICH 24
2. MRI-Based Lesion Evolution and Timepoint Selection 24
3. Baseline Glial and ECM Dynamics Post-ICH 27
3.1 GFAP and Fibronectin Expression Patterns Over Time 27
3.2.GFAP and Iba-1 Expression Patterns Over Time 29
4.Effect of Hydrogel Injection on Lesion Morphology 31
4.1 MRI Assessment of Lesion Evolution Post-Hydrogel Injection 31
4.2 Histological Evaluation of Lesion Repair 33
5.Hydrogel-Mediated Modulation of ECM and Glial Response 35
5.1 Fibronectin and GFAP Through the Time 35
5.2 IBA-1 and GFAP Through the Time 35
6. Behavioral Assessment Reveals Limited Functional Recovery 38
6.1 Ladder Rung Test 40
6.2 Single Pellet Retrieval Test 40
6.3 Cylinder Test 40
IV Discussion 42
V References 45
국문요약 49